12 results on '"Leyla Kavandi"'
Search Results
2. Data from Progesterone Enhances Calcitriol Antitumor Activity by Upregulating Vitamin D Receptor Expression and Promoting Apoptosis in Endometrial Cancer Cells
- Author
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Viqar Syed, Thomas P. Conrads, Gustavo C. Rodriguez, George L. Maxwell, Chad A. Hamilton, Larry G. Thaete, Jane M. Turbov, Guisong Wang, Leyla Kavandi, Brian L. Hood, Huyen Nguyen, Pang-Ning Teng, and Laura R. Lee more...
- Abstract
Human studies suggest that progesterone and calcitriol may prove beneficial in preventing or inhibiting oncogenesis, but the underlying mechanism is not fully understood. The current study investigates the effects of progesterone, calcitriol, and their combination on immortalized human endometrial epithelial cells and endometrial cancer cells and identifies their targets of action. Combination treatment with both agents enhanced vitamin D receptor expression and inhibited cell proliferation through caspase-3 activation and induction of G0–G1 cell-cycle arrest with associated downregulation of cyclins D1 and D3 and p27 induction. We used mass spectrometry–based proteomics to measure protein abundance differences between calcitriol-, progesterone-, or combination-exposed endometrial cells. A total of 117 proteins showed differential expression among these three treatments. Four proteins were then selected for validation studies: histone H1.4 (HIST1H1E), histidine triad nucleotide-binding protein 2 (HINT2), IFN-induced, double-stranded RNA-activated protein kinase (EIF2AK2), and Bcl-2–associated X protein (BAX). Abundance levels of selected candidates were low in endometrial cancer cell lines versus the immortalized endometrial epithelial cell line. All four proteins displayed elevated expression in cancer cells upon exposure to calcitriol, progesterone, or the combination. Further BAX analysis through gain- or loss-of-function experiments revealed that upregulation of BAX decreased cell proliferation by changing the BAX:BCL-2 ratio. Knockdown of BAX attenuated progesterone- and calcitriol-induced cell growth inhibition. Our results showed that progesterone and calcitriol upregulate the expression of BAX along with other apoptosis-related proteins, which induce inhibition of endometrial cancer cell growth by apoptosis and cell-cycle arrest. Cancer Prev Res; 6(7); 731–43. ©2013 AACR. more...
- Published
- 2023
- Full Text
- View/download PDF
Catalog
3. Supplementary Table Part 1 from Progesterone Enhances Calcitriol Antitumor Activity by Upregulating Vitamin D Receptor Expression and Promoting Apoptosis in Endometrial Cancer Cells
- Author
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Viqar Syed, Thomas P. Conrads, Gustavo C. Rodriguez, George L. Maxwell, Chad A. Hamilton, Larry G. Thaete, Jane M. Turbov, Guisong Wang, Leyla Kavandi, Brian L. Hood, Huyen Nguyen, Pang-Ning Teng, and Laura R. Lee more...
- Abstract
Supplementary Table Part 1 - PDF file 319K, Proteins Altered by Progesterone and Calcitiriol. The supplementary table contains the full list of proteins that were found to exhibit differential expression in cancer cell lines following exposure to progesterone and calcitriol more...
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- 2023
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4. The Chinese herbsScutellaria baicalensisandFritillaria cirrhosatarget NFκB to inhibit proliferation of ovarian and endometrial cancer cells
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Yongping Jiang, Viqar Syed, Laura R. Lee, Kashif A. Ahmad, Leyla Kavandi, Amber A. Bokhari, and John E. Pirog
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Cancer Research ,Cell growth ,Endometrial cancer ,Pharmacology ,Biology ,Cell cycle ,medicine.disease ,biology.organism_classification ,IκBα ,Apoptosis ,Cell culture ,Cancer cell ,medicine ,Scutellaria baicalensis ,Molecular Biology - Abstract
The herbs Scutellaria baicalensis (SB) and Fritillaria cirrhosa (FC) are widely used in Chinese medicine to treat several aliments and as an adjuvant to chemotherapy of lung cancer. No information is available regarding the two herbs' influence on ovarian and endometrial cancer. To fill this data gap we compared cell growth responses to SB and FC in ovarian and endometrial cancer cell lines. Dose-dependent cell growth inhibition was observed following higher doses in all cell lines while lower doses stimulated growth in only endometrial cell lines. Higher doses of SB and FC significantly decreased cell growth on soft agar and decreased the invasive potential of cancer cells. Treatment of cells with both herbs resulted in activation of caspase-3, G0/G1 phase cell cycle arrest, downregulation of cyclins D1 and D3 and induction of p27. Both herbs decreased NFκB DNA binding, reduced expression of phosphorylated IκBα, abrogated NFκB activation, and downregulated NFκB-regulated metastasis-promoting proteins in cancer cells. Furthermore, knockdown of NFκB attenuated SB- and FC-induced cell growth inhibition. These results suggest that inhibition of NFκB activation may be an important mechanism for growth suppression by SB and FC. Data indicate that these herbs may represent a new source of agents for NFκB inhibition in cancer therapy. © 2013 Wiley Periodicals, Inc. more...
- Published
- 2013
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5. Progesterone Enhances Calcitriol Antitumor Activity by Upregulating Vitamin D Receptor Expression and Promoting Apoptosis in Endometrial Cancer Cells
- Author
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Larry G. Thaete, Viqar Syed, Thomas P. Conrads, Guisong Wang, Pang-ning Teng, Gustavo C. Rodriguez, Brian L. Hood, Chad A. Hamilton, Jane Turbov, Huyen Nguyen, Leyla Kavandi, Laura R. Lee, and George L. Maxwell more...
- Subjects
Proteomics ,Cancer Research ,medicine.medical_specialty ,Calcitriol ,Blotting, Western ,Apoptosis ,Biology ,medicine.disease_cause ,Calcitriol receptor ,Histones ,Mitochondrial Proteins ,Endometrium ,eIF-2 Kinase ,Bcl-2-associated X protein ,Tandem Mass Spectrometry ,Internal medicine ,Progesterone receptor ,Biomarkers, Tumor ,medicine ,Humans ,Cells, Cultured ,Progesterone ,Cell Proliferation ,bcl-2-Associated X Protein ,Cell growth ,Cell Cycle ,Cell cycle ,Endometrial Neoplasms ,Endocrinology ,Oncology ,Cancer cell ,biology.protein ,Cancer research ,Receptors, Calcitriol ,Female ,Carcinogenesis ,Chromatography, Liquid ,medicine.drug - Abstract
Human studies suggest that progesterone and calcitriol may prove beneficial in preventing or inhibiting oncogenesis, but the underlying mechanism is not fully understood. The current study investigates the effects of progesterone, calcitriol, and their combination on immortalized human endometrial epithelial cells and endometrial cancer cells and identifies their targets of action. Combination treatment with both agents enhanced vitamin D receptor expression and inhibited cell proliferation through caspase-3 activation and induction of G0–G1 cell-cycle arrest with associated downregulation of cyclins D1 and D3 and p27 induction. We used mass spectrometry–based proteomics to measure protein abundance differences between calcitriol-, progesterone-, or combination-exposed endometrial cells. A total of 117 proteins showed differential expression among these three treatments. Four proteins were then selected for validation studies: histone H1.4 (HIST1H1E), histidine triad nucleotide-binding protein 2 (HINT2), IFN-induced, double-stranded RNA-activated protein kinase (EIF2AK2), and Bcl-2–associated X protein (BAX). Abundance levels of selected candidates were low in endometrial cancer cell lines versus the immortalized endometrial epithelial cell line. All four proteins displayed elevated expression in cancer cells upon exposure to calcitriol, progesterone, or the combination. Further BAX analysis through gain- or loss-of-function experiments revealed that upregulation of BAX decreased cell proliferation by changing the BAX:BCL-2 ratio. Knockdown of BAX attenuated progesterone- and calcitriol-induced cell growth inhibition. Our results showed that progesterone and calcitriol upregulate the expression of BAX along with other apoptosis-related proteins, which induce inhibition of endometrial cancer cell growth by apoptosis and cell-cycle arrest. Cancer Prev Res; 6(7); 731–43. ©2013 AACR. more...
- Published
- 2013
- Full Text
- View/download PDF
6. Progesterone and calcitriol attenuate inflammatory cytokines CXCL1 and CXCL2 in ovarian and endometrial cancer cells
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Viqar Syed, Michael A. Collier, Huyen Nguyen, and Leyla Kavandi
- Subjects
medicine.medical_specialty ,Chemokine ,Calcitriol ,Chemokine CXCL1 ,Chemokine CXCL2 ,Antineoplastic Agents ,Inflammation ,Biology ,Transfection ,Biochemistry ,Proinflammatory cytokine ,Metastasis ,NF-KappaB Inhibitor alpha ,Cell Line, Tumor ,Internal medicine ,medicine ,Humans ,Gene Silencing ,Neoplasm Metastasis ,Phosphorylation ,RNA, Small Interfering ,Molecular Biology ,Progesterone ,Ovarian Neoplasms ,Reverse Transcriptase Polymerase Chain Reaction ,Transcription Factor RelA ,Cell Biology ,medicine.disease ,Endometrial Neoplasms ,Gene Expression Regulation, Neoplastic ,CXCL2 ,IκBα ,Endocrinology ,Gene Knockdown Techniques ,Cancer cell ,Cancer research ,biology.protein ,Female ,I-kappa B Proteins ,Drug Screening Assays, Antitumor ,medicine.symptom ,medicine.drug - Abstract
Cytokines/chemokines are key players in cancer-related inflammation. Increasing evidence suggests that chemokines produced by tumor cells are the mediators of metastasis. Thus, agents that can downregulate chemokines expression have potential against cancer metastasis. We have previously shown inhibition of ovarian and endometrial cancer cell growth with progesterone and calcitriol. In the present study, we evaluated the effect of these two agents on the expression of inflammatory genes. Using a RT-PCR array of inflammatory cytokines/chemokines and their receptors, we found a marked attenuation of CXCL1 and CXCL2 (GRO-α and -β) in cancer cells by both treatments. Knockdown of NFκB resulted in a reduced expression of CXCL1 and CXCL2 and the inhibitory effect of progesterone and calcitriol on the expression of chemokines was abrogated in NFκB-silenced cancer cells. Silencing of IκBα increased the expression of CXCL1 and CXCL2 in cancer cells, which can be attributed to the increased activation of NFκB-p65, caused by the lack of its inhibitor. Progesterone and calcitriol-induced inhibition was abolished in IκBα-knockdown cells. Our results demonstrate that suppression of IκBα phosphorylation by progesterone and calcitriol contributes to the reduced expression of CXCL1 and CXCL2. Downregulation of CXCL1 and CXCL2 was associated with a marked inhibition of metastasis-promoting genes. Overall, our results indicate that progesterone and calcitriol inhibit IκBα phosphorylation, NFκB activation, and the expression of NFκB regulated metastasis promoting genes. These results provide attractive data for the possible use of progesterone and calcitriol in the management of endometrial and ovarian tumors. more...
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- 2012
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7. Progesterone and 1,25-Dihydroxyvitamin D3 Inhibit Endometrial Cancer Cell Growth by Upregulating Semaphorin 3B and Semaphorin 3F
- Author
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George L. Maxwell, Vessela S. Ivanova, Viqar Syed, Huyen Nguyen, Gustavo C. Rodriguez, and Leyla Kavandi
- Subjects
Cancer Research ,Receptor complex ,animal structures ,biology ,Angiogenesis ,Endometrial cancer ,Plexin ,medicine.disease ,Metastasis ,Oncology ,Semaphorin ,Cancer cell ,medicine ,biology.protein ,Cancer research ,Ectopic expression ,Molecular Biology - Abstract
Class 3 semaphorins (SEMA), SEMA3B and SEMA3F, are secreted proteins that regulate angiogenesis, tumor growth, and metastasis by binding to their transmembrane receptor complex consisting of plexins and neuropilins (NP). Expression of SEMAs and their receptors was assessed in tissue microarrays by immunohistochemistry. SEMA3B, SEMA3F, and plexin A3 were expressed strongly in normal endometrial tissues, whereas grade-dependent decreases were found in endometrial carcinomas. No change was observed in the expression of plexin A1, NP1, and NP2 in normal versus endometrial cancer tissues. Endometrial cancer cells showed decreased expression of SEMA3B, SEMA3F, and plexin A3 compared with their normal counterparts. Treatment of cancer cells with progesterone (P4) and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] for a period of 72 hours induced a significant upregulation of SEMA3B and SEMA3F as well as inhibited growth of cancer cells by increasing caspase-3 activity. Cotreatment of cell lines with P4 or 1,25(OH)2D3 and their respective antagonists confirmed the specificity of their actions. Transfection of siRNA-targeting SEMA3B and SEMA3F in endometrial cancer cells attenuated P4 or 1,25(OH)2D3-induced growth inhibition. Restoration of SEMA3B or SEMA3F expression in cancer cells caused growth inhibition, reduced soft agar colony formation, and cell invasiveness by inhibiting expression of matrix metalloproteinase-2 (MMP-2), MMP-9, integrin αvβ3, and proangiogenic genes and by upregulating antiangiogenic genes. Thus, we have identified two new P4 and 1,25(OH)2D3-regulated antitumor genes for endometrial cancer. These results suggest that the loss of SEMAs contribute to the malignant phenotype of endometrial cancer cells and that reexpression of SEMAs by ectopic expression or with anticancer agents P4 or 1,25(OH)2D3 can be a promising therapeutic treatment against endometrial cancer. Mol Cancer Res; 9(11); 1479–92. ©2011 AACR. more...
- Published
- 2011
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8. Progesterone and 1,25-dihydroxyvitamin D₃ inhibit endometrial cancer cell growth by upregulating semaphorin 3B and semaphorin 3F
- Author
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Huyen, Nguyen, Vessela S, Ivanova, Leyla, Kavandi, Gustavo C, Rodriguez, George L, Maxwell, and Viqar, Syed
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Membrane Glycoproteins ,Cell Survival ,Membrane Proteins ,Nerve Tissue Proteins ,Receptors, Cell Surface ,Semaphorins ,Transfection ,Immunohistochemistry ,Endometrial Neoplasms ,Up-Regulation ,Cell Line, Tumor ,Humans ,Female ,Vitamin D ,Progesterone - Abstract
Class 3 semaphorins (SEMA), SEMA3B and SEMA3F, are secreted proteins that regulate angiogenesis, tumor growth, and metastasis by binding to their transmembrane receptor complex consisting of plexins and neuropilins (NP). Expression of SEMAs and their receptors was assessed in tissue microarrays by immunohistochemistry. SEMA3B, SEMA3F, and plexin A3 were expressed strongly in normal endometrial tissues, whereas grade-dependent decreases were found in endometrial carcinomas. No change was observed in the expression of plexin A1, NP1, and NP2 in normal versus endometrial cancer tissues. Endometrial cancer cells showed decreased expression of SEMA3B, SEMA3F, and plexin A3 compared with their normal counterparts. Treatment of cancer cells with progesterone (P4) and 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] for a period of 72 hours induced a significant upregulation of SEMA3B and SEMA3F as well as inhibited growth of cancer cells by increasing caspase-3 activity. Cotreatment of cell lines with P4 or 1,25(OH)(2)D(3) and their respective antagonists confirmed the specificity of their actions. Transfection of siRNA-targeting SEMA3B and SEMA3F in endometrial cancer cells attenuated P4 or 1,25(OH)(2)D(3)-induced growth inhibition. Restoration of SEMA3B or SEMA3F expression in cancer cells caused growth inhibition, reduced soft agar colony formation, and cell invasiveness by inhibiting expression of matrix metalloproteinase-2 (MMP-2), MMP-9, integrin αvβ3, and proangiogenic genes and by upregulating antiangiogenic genes. Thus, we have identified two new P4 and 1,25(OH)(2)D(3)-regulated antitumor genes for endometrial cancer. These results suggest that the loss of SEMAs contribute to the malignant phenotype of endometrial cancer cells and that reexpression of SEMAs by ectopic expression or with anticancer agents P4 or 1,25(OH)(2)D(3) can be a promising therapeutic treatment against endometrial cancer. more...
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- 2011
9. Progesterone Receptor Membrane Component 1 and 2 in Normal and Malignant Endometrial Cells
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Leyla Kavandi, Vessela Stefanova Ivanova, Huyen Nguyen, and Viqar Syed
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- 2011
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10. Abstract 1716: Calcitriol and progesterone synergistically inhibit growth in endometrial cancer cells
- Author
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Chad A. Hamilton, George L. Maxwell, Gustavo C. Rodriguez, Thomas P. Conrads, Leyla Kavandi, Jane Turbov, Brian L. Hood, Huyen Nguyen, Larry G. Thaete, Laura R. Lee, and Viqar Syed
- Subjects
Cancer Research ,medicine.medical_specialty ,Calcitriol ,Chemistry ,Cell growth ,Endometrial cancer ,Cancer ,medicine.disease ,medicine.disease_cause ,Calcitriol receptor ,Endocrinology ,Oncology ,Internal medicine ,Cancer cell ,medicine ,Cancer research ,Carcinogenesis ,G1 phase ,medicine.drug - Abstract
Human studies suggest that progesterone and calcitriol may prove beneficial in preventing or inhibiting oncogenesis, but the underlying mechanism is not fully understood. The current study investigates the effects of progesterone, calcitriol and their combination on immortalized human endometrial epithelial cells and endometrial cancer cells and identifies their targets of action. The combined cell treatment enhanced vitamin D receptor expression and synergistically inhibited cell proliferation through caspase-3 activation and induction of G0/G1 cell cycle arrest with associated down-regulation of cyclin D1, D3 and p27 induction. We used mass spectrometry-based proteomics to measure protein abundance differences between calcitriol-, progesterone-, or combination-exposed endometrial cells. A total of 117 proteins showed differential expression amongst these three treatments. Four proteins were then selected for validation studies: histone H1.4 (HIST1H1E), histidine triad nucleotide-binding protein 2 (HINT2), interferon-induced, double-stranded RNA-activated protein kinase (EIF2AK2), and Bcl-2-associated X protein (BAX). Abundance levels of selected candidates were low in endometrial cancer cell lines versus the immortalized endometrial epithelial cell line. All four proteins displayed elevated expression in cancer cells upon exposure to calcitriol, progesterone or the combination. Further BAX analysis through gain or loss of function experiments revealed that upregulation of BAX decreased cell proliferation by changing the BAX:Bcl2 ratio. Knock down of BAX attenuated progesterone- and calcitriol-induced cell growth inhibition. Our results showed that progesterone and calcitriol up-regulate the expression of BAX along with other apoptosis-related proteins, which induced inhibition of endometrial cancer cell growth by apoptosis and cell cycle arrest. Citation Format: Laura R. Lee, Brian L. Hood, Huyen Nguyen, Leyla Kavandi, Jane M. Turbov, Larry G. Thaete, Chad A. Hamilton, Gustavo C. Rodriguez, George L. Maxwell, Thomas P. Conrads, Viqar Syed. Calcitriol and progesterone synergistically inhibit growth in endometrial cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1716. doi:10.1158/1538-7445.AM2013-1716 more...
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- 2013
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11. Abstract 1412: Progesterone and calcitriol attenuate inflammatory cytokines CXCL1 and -2 in endometrial and ovarian cancer cells
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Huyen Nguyen, Michael A. Collier, Viqar Syed, and Leyla Kavandi
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Cancer Research ,medicine.medical_specialty ,Calcitriol ,business.industry ,medicine.medical_treatment ,Cancer ,Inflammation ,medicine.disease ,Proinflammatory cytokine ,Metastasis ,Endocrinology ,Cytokine ,Oncology ,Internal medicine ,Cancer cell ,medicine ,medicine.symptom ,Ovarian cancer ,business ,medicine.drug - Abstract
Chronic inflammation has been shown to play a critical role in growth of cancers. NF-κB is a transcriptional factor that regulates diverse biological processes, including cell proliferation, survival and inflammation. We have previously shown inhibition of endometrial and ovarian cancer cell growth with progesterone and calcitriol. In the present study, we evaluated the effect of progesterone and calcitriol on the expression of inflammatory genes. Using RT-PCR array of inflammatory cytokine and receptor genes, we found two inflammatory cytokines, CXCL1 and -2 (GRO-A and -B), downregulated by both treatments. PCR array results were validated by Western blotting. Knockdown of NF-kB resulted in a reduced expression of CXCL1 and -2 and the inhibitory effect of progesterone and calcitriol on the expression of cytokines was abrogated in NF-kB-silenced cancer cells. Silencing of IkBα increased the expression of CXCL1 and -2 in cancer cells, which can be attributed to the increased activation of NF-kB-p65, caused by the lack of its inhibitor. Progesterone and calcitriol-induced inhibition was abolished in IkBα-knockdown cells. Our results demonstrate that suppression of IkBα phosphorylation by progesterone and calcitriol contributes to the reduced expression of CXCL1 and -2. We investigated the effect of CXCL1 and -2 downregulation on metastasis-promoting genes and found a marked inhibition of CXCR4, COX2 and matrix metalloproteinases (MMP2 and MPP-9). Overall, our results indicate that progesterone and calcitriol downregulate NF-kB in cancer cells, leading to the suppression of metastasis, thus providing the molecular basis for the treatment of endometrial and ovarian cancer patients with progesterone and calcitriol. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1412. doi:1538-7445.AM2012-1412 more...
- Published
- 2012
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- View/download PDF
12. Abstract 4549: Expression and localization of progesterone receptor membrane component 1 and 2 in normal and malignant endometrial cells
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Viqar Syed, Huyen Nguyen, Vessela S. Ivanova, and Leyla Kavandi
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Endometrial cancer ,Cancer ,Biology ,medicine.disease ,medicine.disease_cause ,Oncology ,Cell culture ,Progesterone receptor ,Cancer cell ,medicine ,Cancer research ,Immunohistochemistry ,Carcinogenesis ,PGRMC1 - Abstract
Recently, two progesterone receptor membrane components (PGRMC) have been identified. PGRMC-1 protein has been shown to be overexpressed in breast, colon, and thyroid cancers, whereas far less is known about PGRMC2. The purpose of this study was to assess the expression, localization and hormonal regulation of PGRMC-1 and PGRMC-2 in normal and malignant endometrial tissues and cell lines. Immunohistochemical analysis showed a high expression of PGRMC-1 in normal tissues and a stage dependent decrease was observed in endometrial cancer tissues. A progressive decrease of PGRMC-2 expression was evident in endometrial cancer tissues but was not as marked as in PGRMC-1. Dual immunofluorescent confocal microscopy demonstrated colocalization of PGRMC-1 and PGRMC-2 in the cytoplasm and nucleus of endometrial cancer (Ishikawa and ACI-126) cells. Of significance, in normal epithelial endometrial (NEE) cells PGRMC-2 was predominantly localized in the membrane, whereas PGRMC-1 showed cytoplasmic and nuclear expression. Treatment of cancer cells with progesterone (P4) translocated both PGRMCs to the nucleus, while in normal cells PGRMC-1, but not PGRMC2 was translocated to the nucleus of cells. The results suggest that expression of PGRMCs is regulated by P4 and the dynamic pattern of PGRMC1 and PGRMC2 expression in normal and malignant cells implicate their role in tumorigenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4549. doi:10.1158/1538-7445.AM2011-4549 more...
- Published
- 2011
- Full Text
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