Search

Your search keyword '"genetics, Tumor Suppressor Protein p53"' showing total 2 results
Start Over Descriptor "genetics, Tumor Suppressor Protein p53"
2 results on '"genetics, Tumor Suppressor Protein p53"'

1. p53 regulates epithelial–mesenchymal transition through microRNAs targeting ZEB1 and ZEB2

Author

Young-Jun Jeon, Flavia Pichiorri, Angelo Veronese, Pascal Pineau, Anne Dejean, Tae Jin Lee, Hansjuerg Alder, Agnès Marchio, Stefano Volinia, Taewan Kim, Jeff Palatini, Chang Gong Liu, Sung Suk Suh, Carlo M. Croce, Comprehensive Cancer Center [Colombus], Ohio State University [Columbus] (OSU), Molecular, Cellular, and Developmental Biology Program [Columbus] (MCDB), Organisation Nucléaire et Oncogenèse, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was funded by National Cancer Institute grant RC2 CA148302., We thank Dr. B. Vogelstein for p53+/+ and p53−/− RKO cells, Dr. Gustavo Leone for p53+/+ and p53−/− MEFs, Dr. Gregory J. Goodall for pCIneo-hRL-ZEB1/2 constructs, and Dr. Anders H. Lund for pcDNA3-Zeb2-HA constructs. We also thank Dr. Kay Huebner (The Ohio State University), Dr. Thomas D. Schmittgen (The Ohio State University), and Susan Lutz for careful editing of this paper, and Sharon Palko and Dorothee Wernicke-Jameson for the administrative support., Pineau, Pascal, and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, MESH: Zinc Finger E-box-Binding Homeobox 1, genetics/metabolism, biosynthesis/genetics, Metastasis, genetics/metabolism/pathology, 0302 clinical medicine, MESH: Liver Neoplasms, Immunology and Allergy, genetics, RNA, Neoplasm, Neoplasm Metastasis, MESH: Carcinoma, Hepatocellular, MESH: Tumor Suppressor Protein p53, 0303 health sciences, digestive, oral, and skin physiology, Liver Neoplasms, Hep G2 Cells, MESH: Gene Expression Regulation, Neoplastic, MESH: Transcription Factors, Gene Expression Regulation, Neoplastic, MESH: Repressor Proteins, 030220 oncology & carcinogenesis, embryonic structures, Female, Transcriptional Activation, Carcinoma, Hepatocellular, Epithelial-Mesenchymal Transition, Immunology, Repressor, MESH: Hep G2 Cells, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, 03 medical and health sciences, MESH: Gene Expression Profiling, [SDV.CAN] Life Sciences [q-bio]/Cancer, microRNA, MESH: Homeodomain Proteins, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Epithelial–mesenchymal transition, Transcription factor, Zinc Finger E-box Binding Homeobox 2, 030304 developmental biology, MESH: Zinc Finger E-box Binding Homeobox 2, Homeodomain Proteins, Neoplastic, MESH: Humans, Gene Expression Profiling, Carcinoma, Brief Definitive Report, Zinc Finger E-box-Binding Homeobox 1, Hepatocellular, Cell Biology, HCCS, medicine.disease, MESH: RNA, Neoplasm, MESH: Neoplasm Metastasis, MESH: Male, Repressor Proteins, Gene expression profiling, MicroRNAs, MESH: Epithelial-Mesenchymal Transition, Gene Expression Regulation, Tumor progression, Cancer research, RNA, Neoplasm, MESH: Transcriptional Activation, genetics/metabolism/pathology, Epithelial-Mesenchymal Transition, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Hep G2 Cells, Homeodomain Proteins, biosynthesis/genetics, Humans, Liver Neoplasms, genetics/metabolism/pathology, Male, MicroRNAs, genetics/metabolism, Neoplasm Metastasis, RNA, genetics/metabolism, Repressor Proteins, biosynthesis/genetics, Transcription Factors, biosynthesis/genetics, Transcriptional Activation, genetics, Tumor Suppressor Protein p53, Tumor Suppressor Protein p53, MESH: Female, MESH: MicroRNAs, 030215 immunology, Transcription Factors
Abstract

By transactivating expression of miRNAs that repress expression of the ZEB1 and ZEB2 transcription factors, p53 inhibits the epithelial–mesenchymal transition., p53 suppresses tumor progression and metastasis. Epithelial–mesenchymal transition (EMT) is a key process in tumor progression and metastasis. The transcription factors ZEB1 and ZEB2 promote EMT. Here, we show that p53 suppresses EMT by repressing expression of ZEB1 and ZEB2. By profiling 92 primary hepatocellular carcinomas (HCCs) and 9 HCC cell lines, we found that p53 up-regulates microRNAs (miRNAs), including miR-200 and miR-192 family members. The miR-200 family members transactivated by p53 then repress ZEB1/2 expression. p53-regulated miR-192 family members also repress ZEB2 expression. Inhibition or overexpression of the miRNAs affects p53-regulated EMT by altering ZEB1 and ZEB2 expression. Our findings indicate that p53 can regulate EMT, and that p53-regulated miRNAs are critical mediators of p53-regulated EMT.

Published
2011

2. Mutations of the SF3B1 splicing factor in chronic lymphocytic leukemia: association with progression and fludarabine-refractoriness

Author

Ernesto Gargiulo, Silvia Rasi, Valter Gattei, Valeria Spina, Ilaria Del Giudice, Robin Foà, Marco Fangazio, Michaela Cerri, Hossein Khiabanian, Silvia Deaglio, Davide Rossi, Raul Rabadan, Clara Deambrogi, Tiziana Vaisitti, Francesco Forconi, Gianluca Gaidano, Sabina Chiaretti, Laura Pasqualucci, Stefania Cresta, Monica Messina, Francesco Bertoni, Anna Guarini, Sara Monti, Riccardo Dalla-Favera, and Alessio Bruscaggin

Subjects
Clinical Trials and Observations, Chronic lymphocytic leukemia, DNA Mutational Analysis, Drug Resistance, Sequence Homology, Biochemistry, analogs /&/ derivatives/therapeutic use, hemic and lymphatic diseases, Missense mutation, genetics, Chronic, In Situ Hybridization, Fluorescence, In Situ Hybridization, Oligonucleotide Array Sequence Analysis, Leukemic, Genetics, drug therapy/genetics/pathology, Leukemia, Gene Expression Regulation, Leukemic, Single Nucleotide, Hematology, chronic lymphocytic leukemia mutations SF3B1, Lymphocytic, Fludarabine, Amino Acid Sequence, Antineoplastic Agents, therapeutic use, DNA Mutational Analysis, Disease Progression, Drug Resistance, Neoplasm, Gene Expression Profiling, Gene Expression Regulation, Leukemic, Humans, In Situ Hybridization, Fluorescence, Karyotyping, Leukemia, B-Cell, drug therapy/genetics/pathology, Molecular Sequence Data, Mutation, Oligonucleotide Array Sequence Analysis, Phosphoproteins, genetics, Polymorphism, Single Nucleotide, Ribonucleoprotein, U2 Small Nuclear, genetics, Sequence Homology, Amino Acid, Spliceosomes, genetics, Tumor Suppressor Protein p53, genetics, Vidarabine, Amino Acid, RNA splicing, Disease Progression, RNA Splicing Factors, Vidarabine, medicine.drug, Spliceosome, Molecular Sequence Data, Immunology, Antineoplastic Agents, Biology, Polymorphism, Single Nucleotide, Fluorescence, Splicing factor, medicine, Humans, Amino Acid Sequence, Polymorphism, Sequence Homology, Amino Acid, Gene Expression Profiling, Ribonucleoprotein, Cell Biology, Ribonucleoprotein, U2 Small Nuclear, Phosphoproteins, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Gene Expression Regulation, Drug Resistance, Neoplasm, therapeutic use, Karyotyping, Mutation, Spliceosomes, Cancer research, Neoplasm, Tumor Suppressor Protein p53
Abstract

The genetic lesions identified in chronic lymphocytic leukemia (CLL) do not entirely recapitulate the disease pathogenesis and the development of serious complications, such as chemorefractoriness. While investigating the coding genome of fludarabine-refractory CLL, we observed that mutations of SF3B1, encoding a splicing factor and representing a critical component of the cell spliceosome, were recurrent in 10 of 59 (17%) fludarabine-refractory cases, with a frequency significantly greater than that observed in a consecutive CLL cohort sampled at diagnosis (17/301, 5%; P = .002). Mutations were somatically acquired, were generally represented by missense nucleotide changes, clustered in selected HEAT repeats of the SF3B1 protein, recurrently targeted 3 hotspots (codons 662, 666, and 700), and were predictive of a poor prognosis. In fludarabine-refractory CLL, SF3B1 mutations and TP53 disruption distributed in a mutually exclusive fashion (P = .046). The identification of SF3B1 mutations points to splicing regulation as a novel pathogenetic mechanism of potential clinical relevance in CLL.

Published
2011

Catalog

Books, media, physical & digital resources
See catalog results