22 results on '"Marie Kannius-Janson"'
Search Results
2. Expression patterns and subcellular localization of carbonic anhydrases are developmentally regulated during tooth formation.
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Claes-Göran Reibring, Maha El Shahawy, Kristina Hallberg, Marie Kannius-Janson, Jeanette Nilsson, Seppo Parkkila, William S Sly, Abdul Waheed, Anders Linde, and Amel Gritli-Linde
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Medicine ,Science - Abstract
Carbonic anhydrases (CAs) play fundamental roles in several physiological events, and emerging evidence points at their involvement in an array of disorders, including cancer. The expression of CAs in the different cells of teeth is unknown, let alone their expression patterns during odontogenesis. As a first step towards understanding the role of CAs during odontogenesis, we used immunohistochemistry, histochemistry and in situ hybridization to reveal hitherto unknown dynamic distribution patterns of eight CAs in mice. The most salient findings include expression of CAII/Car2 not only in maturation-stage ameloblasts (MA) but also in the papillary layer, dental papilla mesenchyme, odontoblasts and the epithelial rests of Malassez. We uncovered that the latter form lace-like networks around incisors; hitherto these have been known to occur only in molars. All CAs studied were produced by MA, however CAIV, CAIX and CARPXI proteins were distinctly enriched in the ruffled membrane of the ruffled MA but exhibited a homogeneous distribution in smooth-ended MA. While CAIV, CAVI/Car6, CAIX, CARPXI and CAXIV were produced by all odontoblasts, CAIII distribution displayed a striking asymmetry, in that it was virtually confined to odontoblasts in the root of molars and root analog of incisors. Remarkably, from initiation until near completion of odontogenesis and in several other tissues, CAXIII localized mainly in intracellular punctae/vesicles that we show to overlap with LAMP-1- and LAMP-2-positive vesicles, suggesting that CAXIII localizes within lysosomes. We showed that expression of CAs in developing teeth is not confined to cells involved in biomineralization, pointing at their participation in other biological events. Finally, we uncovered novel sites of CA expression, including the developing brain and eye, the olfactory epithelium, melanoblasts, tongue, notochord, nucleus pulposus and sebaceous glands. Our study provides important information for future single or multiple gene targeting strategies aiming at deciphering the function of CAs during odontogenesis.
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- 2014
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3. Data from Nuclear Janus-Activated Kinase 2/Nuclear Factor 1-C2 Suppresses Tumorigenesis and Epithelial-to-Mesenchymal Transition by Repressing Forkhead Box F1
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Marie Kannius-Janson, Peter Carlsson, Mårten Fernö, Gunnar Bjursell, Pär-Ola Bendahl, Anikó Kovács, Khalil Helou, and Jeanette Nilsson
- Abstract
Progression to metastasis is the proximal cause of most cancer-related mortality. Yet much remains to be understood about what determines the spread of tumor cells. This paper describes a novel pathway in breast cancer that regulates epithelial-to-mesenchymal transition (EMT), motility, and invasiveness. We identify two transcription factors, nuclear factor 1-C2 (NF1-C2) and Forkhead box F1 (FoxF1), downstream of prolactin/nuclear Janus-activated kinase 2, with opposite effects on these processes. We show that NF1-C2 is lost during mammary tumor progression and is almost invariably absent from lymph node metastases. NF1-C2 levels in primary tumors correlate with better patient survival. Manipulation of NF1-C2 levels by expression of a stabilized version or using small interfering RNA showed that NF1-C2 counteracts EMT, motility, invasiveness, and tumor growth. FoxF1 was found to be a direct repressed target of NF1-C2. We provide the first evidence for a role of FoxF1 in cancer and in the regulation of EMT in cells of epithelial origin. Overexpression of FoxF1 was associated with a mesenchymal phenotype, increased invasiveness in vitro, and enhanced growth of breast carcinoma xenografts in nude mice. The relevance of these findings is strengthened by the correlation between FoxF1 expression and a mesenchymal phenoype in breast cancer cell isolates, consistent with the interpretation that FoxF1 promotes invasion and metastasis. Cancer Res; 70(5); 2020–9
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- 2023
4. Supplementary Table from Nuclear Janus-Activated Kinase 2/Nuclear Factor 1-C2 Suppresses Tumorigenesis and Epithelial-to-Mesenchymal Transition by Repressing Forkhead Box F1
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Marie Kannius-Janson, Peter Carlsson, Mårten Fernö, Gunnar Bjursell, Pär-Ola Bendahl, Anikó Kovács, Khalil Helou, and Jeanette Nilsson
- Abstract
Supplementary Table from Nuclear Janus-Activated Kinase 2/Nuclear Factor 1-C2 Suppresses Tumorigenesis and Epithelial-to-Mesenchymal Transition by Repressing Forkhead Box F1
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- 2023
5. Supplementary Figure 1 from Nuclear Janus-Activated Kinase 2/Nuclear Factor 1-C2 Suppresses Tumorigenesis and Epithelial-to-Mesenchymal Transition by Repressing Forkhead Box F1
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Marie Kannius-Janson, Peter Carlsson, Mårten Fernö, Gunnar Bjursell, Pär-Ola Bendahl, Anikó Kovács, Khalil Helou, and Jeanette Nilsson
- Abstract
Supplementary Figure 1 from Nuclear Janus-Activated Kinase 2/Nuclear Factor 1-C2 Suppresses Tumorigenesis and Epithelial-to-Mesenchymal Transition by Repressing Forkhead Box F1
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- 2023
6. Supplementary Figure Legend from Nuclear Janus-Activated Kinase 2/Nuclear Factor 1-C2 Suppresses Tumorigenesis and Epithelial-to-Mesenchymal Transition by Repressing Forkhead Box F1
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Marie Kannius-Janson, Peter Carlsson, Mårten Fernö, Gunnar Bjursell, Pär-Ola Bendahl, Anikó Kovács, Khalil Helou, and Jeanette Nilsson
- Abstract
Supplementary Figure Legend from Nuclear Janus-Activated Kinase 2/Nuclear Factor 1-C2 Suppresses Tumorigenesis and Epithelial-to-Mesenchymal Transition by Repressing Forkhead Box F1
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- 2023
7. Supplementary Movie 1 from Nuclear Janus-Activated Kinase 2/Nuclear Factor 1-C2 Suppresses Tumorigenesis and Epithelial-to-Mesenchymal Transition by Repressing Forkhead Box F1
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Marie Kannius-Janson, Peter Carlsson, Mårten Fernö, Gunnar Bjursell, Pär-Ola Bendahl, Anikó Kovács, Khalil Helou, and Jeanette Nilsson
- Abstract
Supplementary Movie 1 from Nuclear Janus-Activated Kinase 2/Nuclear Factor 1-C2 Suppresses Tumorigenesis and Epithelial-to-Mesenchymal Transition by Repressing Forkhead Box F1
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- 2023
8. Supplementary Movie Legends 1-2 from Nuclear Janus-Activated Kinase 2/Nuclear Factor 1-C2 Suppresses Tumorigenesis and Epithelial-to-Mesenchymal Transition by Repressing Forkhead Box F1
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Marie Kannius-Janson, Peter Carlsson, Mårten Fernö, Gunnar Bjursell, Pär-Ola Bendahl, Anikó Kovács, Khalil Helou, and Jeanette Nilsson
- Abstract
Supplementary Movie Legends 1-2 from Nuclear Janus-Activated Kinase 2/Nuclear Factor 1-C2 Suppresses Tumorigenesis and Epithelial-to-Mesenchymal Transition by Repressing Forkhead Box F1
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- 2023
9. Supplementary Methods from Nuclear Janus-Activated Kinase 2/Nuclear Factor 1-C2 Suppresses Tumorigenesis and Epithelial-to-Mesenchymal Transition by Repressing Forkhead Box F1
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Marie Kannius-Janson, Peter Carlsson, Mårten Fernö, Gunnar Bjursell, Pär-Ola Bendahl, Anikó Kovács, Khalil Helou, and Jeanette Nilsson
- Abstract
Supplementary Methods from Nuclear Janus-Activated Kinase 2/Nuclear Factor 1-C2 Suppresses Tumorigenesis and Epithelial-to-Mesenchymal Transition by Repressing Forkhead Box F1
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- 2023
10. Supplementary Movie 2 from Nuclear Janus-Activated Kinase 2/Nuclear Factor 1-C2 Suppresses Tumorigenesis and Epithelial-to-Mesenchymal Transition by Repressing Forkhead Box F1
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Marie Kannius-Janson, Peter Carlsson, Mårten Fernö, Gunnar Bjursell, Pär-Ola Bendahl, Anikó Kovács, Khalil Helou, and Jeanette Nilsson
- Abstract
Supplementary Movie 2 from Nuclear Janus-Activated Kinase 2/Nuclear Factor 1-C2 Suppresses Tumorigenesis and Epithelial-to-Mesenchymal Transition by Repressing Forkhead Box F1
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- 2023
11. Supplementary Table Legend from Nuclear Janus-Activated Kinase 2/Nuclear Factor 1-C2 Suppresses Tumorigenesis and Epithelial-to-Mesenchymal Transition by Repressing Forkhead Box F1
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Marie Kannius-Janson, Peter Carlsson, Mårten Fernö, Gunnar Bjursell, Pär-Ola Bendahl, Anikó Kovács, Khalil Helou, and Jeanette Nilsson
- Abstract
Supplementary Table Legend from Nuclear Janus-Activated Kinase 2/Nuclear Factor 1-C2 Suppresses Tumorigenesis and Epithelial-to-Mesenchymal Transition by Repressing Forkhead Box F1
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- 2023
12. Loss of E-cadherin expression is not a prerequisite for c-erbB2-induced epithelial-mesenchymal transition
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Marie Kannius-Janson, Dan Baeckström, Noreen Akhtar, and Gisela Nilsson
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Cancer Research ,Epithelial-Mesenchymal Transition ,Receptor, ErbB-2 ,Receptor tyrosine kinase ,Cell Line ,breast cancer ,vimentin ,Downregulation and upregulation ,Cell Adhesion ,Humans ,Epithelial–mesenchymal transition ,Mammary Glands, Human ,Cell adhesion ,Cytoskeleton ,mammary epithelium ,biology ,Cadherin ,Transdifferentiation ,Epithelial Cells ,Articles ,Fibroblasts ,Tetracycline ,Cadherins ,Cell biology ,epidermal growth factor receptor family ,Gene Expression Regulation ,Oncology ,cell-cell adhesion ,embryonic structures ,biology.protein ,Ectopic expression ,Signal transduction ,Signal Transduction ,cell density - Abstract
Recent research into the mechanisms of tumour cell invasiveness has highlighted the parallels between carcinogenesis and epithelial-mesenchymal transition (EMT), originally described as a developmental transdifferentiation program but also implicated in fibrosis and cancer. In a model system for mammary carcinogenesis, we previously observed that induced signalling from a homodimer of the c-erbB2 (HER2) receptor tyrosine kinase in an initially non-malignant mammary cell line caused EMT where i) cell scattering occurred before downregulation of the cell-cell adhesion molecule E-cadherin and ii) the progress of EMT was dramatically delayed when cells were grown at high density. Here, we have further analysed these phenomena. Ectopic expression of E-cadherin concomitant with c-erbB2 signalling was unable to impede the progression of EMT, suggesting that E-cadherin downregulation is not required for EMT. Furthermore, fibroblast-like cells isolated after EMT induced in the presence or absence of ectopic E-cadherin expression showed highly similar morphology and vimentin expression. E-cadherin expressed in these fibroblastic cells had a subcellular localisation similar to that found in epithelial cells, but it exhibited a much weaker attachment to the cytoskeleton, suggesting cytoskeletal rearrangements as an important mechanism in EMT-associated cell scattering. We also investigated whether density-dependent inhibition of EMT is mediated by E-cadherin as a sensor for cell-cell contact, by expressing dominant-negative E-cadherin. While expression of this mutant weakened cell-cell adhesion, it failed to facilitate EMT at high cell densities. These results indicate that loss of E-cadherin expression is a consequence rather than a cause of c-erbB2-induced EMT and that density-dependent inhibition of EMT is not mediated by E-cadherin signalling.
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- 2014
13. Nuclear Jak2 and Transcription Factor NF1-C2: a Novel Mechanism of Prolactin Signaling in Mammary Epithelial Cells
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Marie Kannius-Janson, Gunnar Bjursell, and Jeanette Nilsson
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Proteasome Endopeptidase Complex ,Cell Line ,Mice ,chemistry.chemical_compound ,Proto-Oncogene Proteins ,Two-Hybrid System Techniques ,hemic and lymphatic diseases ,Animals ,Humans ,Phosphorylation ,Mammary Glands, Human ,Molecular Biology ,Transcription factor ,STAT5 ,Cell Nucleus ,Janus kinase 2 ,biology ,food and beverages ,Epithelial Cells ,Tyrosine phosphorylation ,Lipase ,Articles ,Cell Biology ,Janus Kinase 2 ,Protein-Tyrosine Kinases ,Molecular biology ,Prolactin ,NFI Transcription Factors ,chemistry ,biology.protein ,STAT protein ,Tyrosine ,RNA Interference ,Tumor Suppressor Protein p53 ,hormones, hormone substitutes, and hormone antagonists ,Nuclear localization sequence ,Signal Transduction - Abstract
The classical mechanism by which prolactin transduces its signal in mammary epithelial cells is by activation of cytosolic signal transducer and activator of transcription 5 (Stat5) via a plasma membrane-associated prolactin receptor-Janus kinase 2 (Jak2) complex. Here we describe an alternative pathway through which prolactin via Jak2 localized in the nucleus activates the transcription factor nuclear factor 1-C2 (NF1-C2). Previous reports have demonstrated a nuclear localization of Jak2, but the physiologic importance of nuclear Jak2 has not been clear. We demonstrate that nuclear Jak2 regulates the amount of active NF1-C2 through tyrosine phosphorylation and proteasomal degradation. Our data also demonstrate a link between prolactin and p53 as well as the milk gene carboxyl ester lipase through nuclear Jak2 and NF1-C2. Hence, we describe a novel pathway through which nuclear Jak2 is subject to regulation by prolactin in mammary epithelial cells.
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- 2006
14. The p53 tumor suppressor gene is regulated in vivo by nuclear factor 1-C2 in the mouse mammary gland during pregnancy
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Marie Kannius-Janson, Eva Johansson, Gunnar Bjursell, and Jeanette Nilsson
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Transcriptional Activation ,Gene isoform ,congenital, hereditary, and neonatal diseases and abnormalities ,Cancer Research ,Tumor suppressor gene ,Mammary gland ,Oligonucleotides ,Mice, Inbred Strains ,Biology ,Mice ,Mammary Glands, Animal ,Pregnancy ,Gene expression ,Genetics ,Transcriptional regulation ,medicine ,Animals ,Protein Isoforms ,Promoter Regions, Genetic ,Molecular Biology ,Gene ,Cells, Cultured ,Regulation of gene expression ,Binding Sites ,Nuclear Proteins ,Epithelial Cells ,DNA-Binding Proteins ,NFI Transcription Factors ,medicine.anatomical_structure ,Gene Expression Regulation ,Genetic Techniques ,CCAAT-Enhancer-Binding Proteins ,Cancer research ,Pregnancy, Animal ,Female ,Y-Box-Binding Protein 1 ,Tumor Suppressor Protein p53 ,Chromatin immunoprecipitation ,Transcription Factors - Abstract
The p53 tumor suppressor protein plays an important role in preventing cancer development by arresting or killing potential tumor cells. Downregulated p53 levels, or mutations within the p53 gene, leading to the loss of p53 activity, are found in many breast carcinomas. Here we demonstrate that the p53 gene is transcriptionally upregulated in the normal mouse mammary gland at midpregnancy. We show that the specific isoform nuclear factor 1-C2 (NF1-C2) plays an important role in this activation. Functional mutation of the NF1-binding site in the mouse p53 promoter resulted in a reduction of the gene expression to less than 30% in mammary epithelial cells. By the use of two powerful techniques, chromatin immunoprecipitation and oligonucleotide decoy, we verify the importance of NF1-C2 in p53 gene activation in vivo. These findings demonstrate a broader role for NF1-C2 in the mammary gland at midpregnancy, beyond its earlier reported activation of milk protein genes. We also demonstrate that NF1-A1 proteins are produced in the mouse mammary gland. However, due to their lower affinity to the NF1-binding site, these proteins are not involved in the transcriptional upregulation of p53 at midpregnancy. This paper constitutes the first report demonstrating the importance of NF1 proteins in the p53 gene activation in the mouse mammary gland. It is also the first time that p53 gene activation is coupled to a specific, endogenously expressed NF1 isoform.
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- 2003
15. The tissue-specific regulation of the carboxyl ester lipase gene in exocrine pancreas differs significantly between mouse and human
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Jeanette Nilsson, Marie Kannius-Janson, Ulf Lidberg, and Gunnar Bjursell
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Amino Acid Motifs ,Molecular Sequence Data ,Plasma protein binding ,Transfection ,Biochemistry ,Carboxylesterase ,Cell Line ,Mice ,Genes, Reporter ,Sequence Homology, Nucleic Acid ,Tumor Cells, Cultured ,Animals ,Humans ,Tissue Distribution ,Cloning, Molecular ,Lipase ,Binding site ,Promoter Regions, Genetic ,Enhancer ,Pancreas ,Molecular Biology ,Gene ,Transcription factor ,Cell Nucleus ,Binding Sites ,Base Sequence ,biology ,Ccaat-enhancer-binding proteins ,Cell Biology ,Fibroblasts ,Blotting, Northern ,Molecular biology ,Rats ,Enhancer Elements, Genetic ,Mutation ,CCAAT-Enhancer-Binding Proteins ,biology.protein ,Carboxylic Ester Hydrolases ,Research Article ,Protein Binding ,Transcription Factors - Abstract
The carboxyl ester lipase (CEL) gene is highly expressed in exocrine pancreas and expression of the human CEL gene is mediated by a strong tissue-specific enhancer, which is absolutely necessary for high-level expression. The mouse promoter, on the other hand, does not contain a corresponding enhancer element, but instead is totally dependent on another pancreas-specific element. This element is identified as a pancreatic transcription factor 1 (PTF 1)-binding site. The human CEL promoter also contains a putative PTF 1 element located at a position corresponding to the essential PTF 1 site in the mouse promoter. However, nucleotide changes in the human promoter 5´ flanking this PTF 1 site have created an overlapping CCAAT/enhancer-binding protein (C/EBP)-like binding motif, interfering with the binding of PTF 1. Hence, our findings provide an example of genetic divergence between species not accompanied by difference in function.
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- 2000
16. Studies of the regulation of the mouse carboxyl ester lipase gene in mammary gland
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Amel Gritli-Linde, Ulf Lidberg, Gunnar Bjursell, Marie Kannius-Janson, Jeanette Nilsson, and Kåre Hultén
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Gene isoform ,Molecular Sequence Data ,DNA Footprinting ,Biochemistry ,Gene Expression Regulation, Enzymologic ,Carboxylesterase ,Cell Line ,Mice ,Mammary Glands, Animal ,Pregnancy ,Gene expression ,STAT5 Transcription Factor ,Animals ,Promoter Regions, Genetic ,Molecular Biology ,Gene ,Transcription factor ,STAT5 ,Binding Sites ,Neurofibromin 1 ,Base Sequence ,biology ,Proteins ,Promoter ,Cell Biology ,Milk Proteins ,Molecular biology ,DNA-Binding Proteins ,Mice, Inbred C57BL ,Trans-Activators ,biology.protein ,STAT protein ,Female ,Whey Acidic Protein ,Carboxylic Ester Hydrolases ,Research Article - Abstract
The lactating mammary gland and pancreas of mouse constitute the main tissues for synthesis and secretion of a bile-salt-stimulated lipase called carboxyl ester lipase (CEL). In this paper we have analysed the endogenous CEL gene expression in mammary gland. It is shown that the gene is expressed at day 14 of pregnancy, which is synchronous with that of the whey acidic protein (WAP) gene. Even though the CEL and WAP genes are induced at the same time during mammary gland differentiation, their regulation is different with respect to dependence on lactogenic hormones. The high induction of the WAP gene expression due to the activation of signal transducer and activator of transcription (STAT)5 by prolactin has not been observed for the CEL gene, even though it has been demonstrated that both STAT5 isoforms interact with one of the γ-interferon activation sequence sites in the promoter of the CEL gene. Hence we have demonstrated that the prolactin/STAT5 signal is not involved in a general and significant activation of ‘milk genes ’. Instead of a direct effect of the lactogenic hormones, the up-regulation of the CEL gene is correlated with an increase in the number of differentiated epithelial cells. Furthermore, promoter studies using the mammary-gland-derived cell line, HC11, show that a major positive element in the CEL gene promoter interacts with a member(s) of the CCAAT-binding transcription factor/nuclear factor 1 family, binding to a palindromic site. Binding of this factor(s) is important for the tissue-specific activation of the CEL gene in the mammary gland, because no activation by this factor(s) was seen in cells of pancreatic origin.
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- 1998
17. Transcriptional Regulation of the Human Carboxyl Ester Lipase Gene in Exocrine Pancreas
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Gunnar Bjursell, Marie Kannius-Janson, Jeanette Annika Nilsson, and Ulf Lidberg
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Regulation of gene expression ,Reporter gene ,Regulatory sequence ,Transcriptional regulation ,Enhancer RNAs ,Cell Biology ,Biology ,Enhancer ,Molecular Biology ,Biochemistry ,Molecular biology ,Transcription factor ,Intestinal absorption - Abstract
The human carboxyl ester lipase (CEL) is an important enzyme for the intestinal absorption of dietary lipids. The gene is highly expressed in exocrine pancreas and in the mammary gland during pregnancy and lactation. In this paper, we have focused on its transcriptional regulation in exocrine pancreas. Reporter gene analysis in cell cultures reveals that a high level of tissue-specific expression is established by the proximal 839 base pairs of the 5'-flanking region. This is due to a strong enhancer, located at -672 to -637. Transfections in mammary gland-derived cells reveal that the enhancer is pancreas-specific and does not contribute to the mammary gland expression. This indicates that the expression of the CEL gene in the mammary gland and pancreas, respectively, is due to two different regulatory systems. Further characterizations of the enhancer reveal that it is composed of two closely located cis-elements. The proximal element mediates a positive effect, whereas the distal element exerts a silencing effect on the positive proximal element. The functional enhancer complex is composed of ubiquitously expressed factors, since similar interactions are achieved with nuclear extracts from cells derived from other tissues. However, no enhancer activity is achieved in such cells. Hence, the net enhancer activity is the result of a tissue-specific balance between factors interacting with the two elements. Since none of the described cis-elements show any clear homology to known cis-elements, we propose that the interacting complex is composed of yet unidentified transcription factors.
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- 1998
18. Segmented regression, a versatile tool to analyze mRNA levels in relation to DNA copy number aberrations
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Toshima Z. Parris, Marie Kannius-Janson, Khalil Helou, Gunnar Steineck, Szilard Nemes, Anna Danielsson, and Junmei Miao Jonasson
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Cancer Research ,Messenger RNA ,Comparative Genomic Hybridization ,Models, Genetic ,Gene Expression Profiling ,Gene Dosage ,Chromosome ,Breast Neoplasms ,Biology ,Molecular biology ,Gene Expression Regulation, Neoplastic ,chemistry.chemical_compound ,Downregulation and upregulation ,chemistry ,Gene duplication ,Gene expression ,Cancer cell ,Genetics ,Humans ,Regression Analysis ,Female ,RNA, Messenger ,Segmented regression ,DNA - Abstract
DNA copy number aberrations (CNA) and subsequent altered gene expression profiles (mRNA levels) are characteristic features of cancerous cells. Integrative genomic analysis aims to identify recurrent CNA that may have a potential role in cancer development, assuming that gene amplification is accompanied by overexpression, while deletions give rise to downregulation of gene expression. We propose a segmented regression-based approach to identify CNA-driven alteration of gene expression profiles. Segmented regression allows to fit piecewise linear models in different domains of CNA joined by a change-point, where the mRNA–CNA relationship undergoes structural changes. Here, we illustrate the implementation and applicability of the proposed model using 1,161 chromosome fragments detected as DNA CNA in primary tumors from 97 breast cancer patients. We identified significant CNA-driven changes in gene expression levels for 341 chromosome fragments, of which 72 showed a nonlinear relationship to CNA. For 59 of 72 chromosome fragments (82%), we observed an initial increase in mRNA levels due to changes in CNA. After the change-point was passed, the mRNA levels reached a plateau, and a further increase in DNA copy numbers did not induce further elevation in mRNA levels. In contrast, for 13 chromosome fragments, the change-point marked the point where mRNA production accelerated. We conclude that segmented regression modeling may provide valuable insights into the impact CNA have on gene expression in cancer cells. © 2011 Wiley Periodicals, Inc.
- Published
- 2011
19. Nuclear factor 1-C2 is regulated by prolactin and shows a distinct expression pattern in the mouse mammary epithelial cells during development
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Eva Johansson, Amel Gritli-Linde, Gunnar Bjursell, Marie Kannius-Janson, and Jeanette Nilsson
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congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Tumor suppressor gene ,Transcription, Genetic ,Mammary gland ,Molecular Sequence Data ,In situ hybridization ,Biology ,Mice ,Endocrinology ,Mammary Glands, Animal ,Pregnancy ,Internal medicine ,Lactation ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Molecular Biology ,Transcription factor ,Cells, Cultured ,Cell Nucleus ,Mice, Knockout ,Immunochemistry ,Gene Expression Regulation, Developmental ,Epithelial Cells ,General Medicine ,Prolactin ,nervous system diseases ,Cell biology ,Cell nucleus ,NFI Transcription Factors ,medicine.anatomical_structure ,biology.protein ,CCAAT-Enhancer-Binding Proteins ,Female ,Whey Acidic Protein ,Transcription Factors - Abstract
We have previously demonstrated that the transcription factor nuclear factor (NF)1-C2 plays an important role in the mammary gland for the activation of the tumor suppressor gene p53. It also activates the milk genes carboxyl ester lipase and whey acidic protein, implying that NF1-C2 participates both in the establishment of a functional gland and in protection of the gland against tumorigenesis during proliferation. In this study, we have developed a new sensitive NF1-C2-specific antiserum for immunohistochemical analyses of the NF1-C2 distribution during mammary gland development. We show that the NF1-C2 protein is present in the epithelial compartment at the virgin stage and throughout mammary gland development. However, in the lactation stage the NF1-C2 protein levels strongly decreased, and many epithelial nuclei stained negative. In situ hybridization shows that NF1-C2 transcripts are expressed in the whole epithelium at pregnancy as well as the lactation stage, indicating that the reduction in protein levels is posttranscriptionally regulated. At involution, the NF1-C2 proteins are back to high levels. Based on studies using NMuMG cells and mammary tissue from heterozygous prolactin receptor knockout mice, we also demonstrate that prolactin has a direct effect in the maintenance of the NF1-C2 protein levels in the mammary epithelial nuclei at the virgin stage and during pregnancy. Hence, we have identified another transcription factor in the mammary gland, besides signal transducer and activator of transcription 5, through which prolactin may control mammary gland development. Furthermore, our data suggest a link between prolactin and p53 in the mammary gland, through NF1-C2.
- Published
- 2005
20. Nuclear factor 1-C2 contributes to the tissue-specific activation of a milk protein gene in the differentiating mammary gland
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Marie Kannius-Janson, Jeanette Nilsson, Eva Johansson, and Gunnar Bjursell
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Gene isoform ,congenital, hereditary, and neonatal diseases and abnormalities ,Blotting, Western ,Biology ,Transfection ,Biochemistry ,Carboxylesterase ,SOX4 ,Mice ,Gene expression ,Tumor Cells, Cultured ,Animals ,Breast ,neoplasms ,Molecular Biology ,Gene ,Transcription factor ,Regulation of gene expression ,Nuclear Proteins ,Promoter ,Cell Differentiation ,Cell Biology ,Y box binding protein 1 ,Milk Proteins ,Molecular biology ,eye diseases ,nervous system diseases ,Rats ,DNA-Binding Proteins ,Mice, Inbred C57BL ,Alternative Splicing ,NFI Transcription Factors ,Gene Expression Regulation ,CCAAT-Enhancer-Binding Proteins ,Mice, Inbred CBA ,Female ,Y-Box-Binding Protein 1 ,Carboxylic Ester Hydrolases ,Transcription Factors - Abstract
Members of the nuclear factor 1 (NF1) transcription factor family have been postulated to be involved in the regulation of milk genes. In this work we have been able to identify the splice variant NF1-C2 as an important member of a tissue-specific activating complex that regulates the milk gene encoding carboxyl ester lipase (CEL). Mutation of the NF1-binding site in the CEL gene promoter results in a drastic reduction of the gene expression to about 15% in mammary epithelial cells. Furthermore, we demonstrate that the NF1-C2 protein interacts with a higher affinity to the NF1-binding site in the CEL gene promoter than other NF1 family members do and that NF1-C2 in the mouse mammary gland is a phosphorylated protein. During development of the mouse mammary gland, binding of NF1-C2 to the CEL gene promoter is induced at midpregnancy, in correlation with the induction of CEL gene expression. The fact that the NF1-C2 involving complex remains throughout the lactation period and decreases during the weaning period, when the CEL gene is down-regulated, supports its importance in the regulation of CEL gene expression. To our knowledge, this is the first report identifying a specific, endogenously expressed NF1 isoform to be involved in the tissue-specific activation of a gene.
- Published
- 2002
21. Expression Patterns and Subcellular Localization of Carbonic Anhydrases Are Developmentally Regulated during Tooth Formation
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Marie Kannius-Janson, Amel Gritli-Linde, Maha El Shahawy, Abdul Waheed, William S. Sly, Seppo Parkkila, Anders Linde, Kristina Hallberg, Claes-Göran Reibring, Jeanette Nilsson, BioMediTech - BioMediTech, and University of Tampere
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Biomineralization ,Pathology ,Physiology ,lcsh:Medicine ,Mice ,Lääketieteen bioteknologia - Medical biotechnology ,Molecular Cell Biology ,Morphogenesis ,Medicine and Health Sciences ,lcsh:Science ,In Situ Hybridization ,Carbonic Anhydrases ,Regulation of gene expression ,Multidisciplinary ,Gene Expression Regulation, Developmental ,Animal Models ,Epithelial cell rests of Malassez ,Immunohistochemistry ,Cell biology ,Isoenzymes ,Protein Transport ,medicine.anatomical_structure ,Organ Specificity ,Odontogenesis ,Anatomy ,Cellular Structures and Organelles ,Ameloblast ,Research Article ,Cell Physiology ,medicine.medical_specialty ,Histology ,Mesenchyme ,Mouse Models ,In situ hybridization ,Biology ,Research and Analysis Methods ,Gene Expression Regulation, Enzymologic ,Model Organisms ,stomatognathic system ,Notochord ,medicine ,Animals ,Dental papilla ,lcsh:R ,Biology and Life Sciences ,Cell Biology ,Molecular Development ,Odontoblast ,Animals, Newborn ,lcsh:Q ,Lysosomes ,Physiological Processes ,Tooth ,Developmental Biology - Abstract
Carbonic anhydrases (CAs) play fundamental roles in several physiological events, and emerging evidence points at their involvement in an array of disorders, including cancer. The expression of CAs in the different cells of teeth is unknown, let alone their expression patterns during odontogenesis. As a first step towards understanding the role of CAs during odontogenesis, we used immunohistochemistry, histochemistry and in situ hybridization to reveal hitherto unknown dynamic distribution patterns of eight CAs in mice. The most salient findings include expression of CAII/Car2 not only in maturation-stage ameloblasts (MA) but also in the papillary layer, dental papilla mesenchyme, odontoblasts and the epithelial rests of Malassez. We uncovered that the latter form lace-like networks around incisors; hitherto these have been known to occur only in molars. All CAs studied were produced by MA, however CAIV, CAIX and CARPXI proteins were distinctly enriched in the ruffled membrane of the ruffled MA but exhibited a homogeneous distribution in smooth-ended MA. While CAIV, CAVI/Car6, CAIX, CARPXI and CAXIV were produced by all odontoblasts, CAIII distribution displayed a striking asymmetry, in that it was virtually confined to odontoblasts in the root of molars and root analog of incisors. Remarkably, from initiation until near completion of odontogenesis and in several other tissues, CAXIII localized mainly in intracellular punctae/vesicles that we show to overlap with LAMP-1- and LAMP-2-positive vesicles, suggesting that CAXIII localizes within lysosomes. We showed that expression of CAs in developing teeth is not confined to cells involved in biomineralization, pointing at their participation in other biological events. Finally, we uncovered novel sites of CA expression, including the developing brain and eye, the olfactory epithelium, melanoblasts, tongue, notochord, nucleus pulposus and sebaceous glands. Our study provides important information for future single or multiple gene targeting strategies aiming at deciphering the function of CAs during odontogenesis. Public Library of Science open access
- Published
- 2014
22. Abnormal Hair Development and Apparent Follicular Transformation to Mammary Gland in the Absence of Hedgehog Signaling
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Amel Gritli-Linde, Jeanette Nilsson, Anders Linde, Kristina Hallberg, Martyn T. Cobourne, Azadeh Reyahi, Marie Kannius-Janson, Andrew P. McMahon, Paul T. Sharpe, and Brian D. Harfe
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Keratinocytes ,medicine.medical_specialty ,Mesoderm ,Cell signaling ,DEVBIO ,Outer root sheath ,General Biochemistry, Genetics and Molecular Biology ,Article ,Receptors, G-Protein-Coupled ,Mice ,Mammary Glands, Animal ,Hair cycle ,Internal medicine ,Ectoderm ,medicine ,Morphogenesis ,Animals ,Hedgehog Proteins ,RNA, Messenger ,Sonic hedgehog ,Molecular Biology ,beta Catenin ,Cell Line, Transformed ,Metaplasia ,Hyperplasia ,biology ,Integrases ,integumentary system ,Stem Cells ,Gene Expression Regulation, Developmental ,Cell Biology ,Hair follicle ,Smoothened Receptor ,Hedgehog signaling pathway ,Cell biology ,medicine.anatomical_structure ,Endocrinology ,Bone Morphogenetic Proteins ,biology.protein ,Smoothened ,Hair Follicle ,Signal Transduction ,Developmental Biology - Abstract
Summary We show that removing the Shh signal tranducer Smoothened from skin epithelium secondarily results in excess Shh levels in the mesenchyme. Moreover, the phenotypes we observe reflect decreased epithelial Shh signaling, yet increased mesenchymal Shh signaling. For example, the latter contributes to exuberant hair follicle (HF) induction, while the former depletes the resulting follicular stem cell niches. This disruption of the niche apparently also allows the remaining stem cells to initiate hair formation at inappropriate times. Thus, the temporal structure of the hair cycle may depend on the physical structure of the niche. Finally, we find that the ablation of epithelial Shh signaling results in unexpected transformations: the follicular outer root sheath takes on an epidermal character, and certain HFs disappear altogether, having adopted a strikingly mammary gland-like fate. Overall, our study uncovers a multifaceted function for Shh in sculpting and maintaining the integrity and identity of the developing HF.
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