دورية أكاديمية
Protein Kinase Cα Modulates Estrogen-Receptor-Dependent Transcription and Proliferation in Endometrial Cancer Cells
العنوان: | Protein Kinase Cα Modulates Estrogen-Receptor-Dependent Transcription and Proliferation in Endometrial Cancer Cells |
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المؤلفون: | Alicia M. Thorne, Twila A. Jackson, Van C. Willis, Andrew P. Bradford |
المصدر: | Obstetrics and Gynecology International, Vol 2013 (2013) |
بيانات النشر: | Wiley, 2013. |
سنة النشر: | 2013 |
المجموعة: | LCC:Gynecology and obstetrics |
مصطلحات موضوعية: | Gynecology and obstetrics, RG1-991 |
الوصف: | Endometrial cancer is the most common invasive gynecologic malignancy in developed countries. The most prevalent endometrioid tumors are linked to excessive estrogen exposure and hyperplasia. However, molecular mechanisms and signaling pathways underlying their etiology and pathophysiology remain poorly understood. We have shown that protein kinase Cα (PKCα) is aberrantly expressed in endometrioid tumors and is an important mediator of endometrial cancer cell survival, proliferation, and invasion. In this study, we demonstrate that expression of active, myristoylated PKCα conferred ligand-independent activation of estrogen-receptor- (ER-) dependent promoters and enhanced responses to estrogen. Conversely, knockdown of PKCα reduced ER-dependent gene expression and inhibited estrogen-induced proliferation of endometrial cancer cells. The ability of PKCα to potentiate estrogen activation of ER-dependent transcription was attenuated by inhibitors of phosphoinositide 3-kinase (PI3K) and Akt. Evidence suggests that PKCα and estrogen signal transduction pathways functionally interact, to modulate ER-dependent growth and transcription. Thus, PKCα signaling, via PI3K/Akt, may be a critical element of the hyperestrogenic environment and activation of ER that is thought to underlie the development of estrogen-dependent endometrial hyperplasia and malignancy. PKCα-dependent pathways may provide much needed prognostic markers of aggressive disease and novel therapeutic targets in ER positive tumors. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1687-9589 1687-9597 31621244 |
Relation: | https://doaj.org/toc/1687-9589; https://doaj.org/toc/1687-9597 |
DOI: | 10.1155/2013/537479 |
URL الوصول: | https://doaj.org/article/d07bbb31621244a488a040e601822c4c |
رقم الأكسشن: | edsdoj.07bbb31621244a488a040e601822c4c |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 16879589 16879597 31621244 |
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DOI: | 10.1155/2013/537479 |