BRCA1 Inhibits Membrane Estrogen and Growth Factor Receptor Signaling to Cell Proliferation in Breast Cancer

BRCA1 mutations and estrogen use are risk factors for the development of breast cancer. Recent work has identified estrogen receptors localized at the plasma membrane that signal to cell biology. We examined the impact of BRCA1 on membrane estrogen and growth factor receptor signaling to breast canc...

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Những tác giả chính: Razandi, Mahnaz, Pedram, Ali, Rosen, Eliot M., Levin, Ellis R.
Định dạng: Bài viết
Ngôn ngữ:English
Được phát hành: American Society for Microbiology 2004
Những chủ đề:
Cell Growth and Development
Truy cập trực tuyến:https://ncbi.nlm.nih.gov/pmc/articles/PMC480898/
https://ncbi.nlm.nih.gov/pubmed/15199145
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1128/MCB.24.13.5900-5913.2004
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spelling pubmed-4808982004-07-23 BRCA1 Inhibits Membrane Estrogen and Growth Factor Receptor Signaling to Cell Proliferation in Breast Cancer Razandi, Mahnaz Pedram, Ali Rosen, Eliot M. Levin, Ellis R. Mol Cell Biol Cell Growth and Development BRCA1 mutations and estrogen use are risk factors for the development of breast cancer. Recent work has identified estrogen receptors localized at the plasma membrane that signal to cell biology. We examined the impact of BRCA1 on membrane estrogen and growth factor receptor signaling to breast cancer cell proliferation. MCF-7 and ZR-75-1 cells showed a rapid and sustained activation of extracellular signal-related kinase (ERK) in response to estradiol (E2) that was substantially prevented by wild-type (wt) but not mutant BRCA1. The proliferation of MCF-7 cells induced by E2 was significantly inhibited by PD98059, a specific ERK inhibitor, or by dominant negative ERK2 expression and by expression of wt BRCA1 (but not mutant BRCA1). E2 induced the synthesis of cyclins D1 and B1, the activity of cyclin-dependent kinases Cdk4 and CDK1, and G(1)/S and G(2)/M cell cycle progression. The intact tumor suppressor inhibited all of these. wt BRCA1 also inhibited epidermal growth factor and insulin-like growth factor I-induced ERK and cell proliferation. The inhibition of ERK and cell proliferation by BRCA1 was prevented by phosphatase inhibitors and by interfering RNA knockdown of the ERK phosphatase, mitogen-activated kinase phosphatase 1. Our findings support a novel tumor suppressor function of BRCA1 that is relevant to breast cancer and identify a potential interactive risk factor for women with BRCA1 mutations. American Society for Microbiology 2004-07 /pmc/articles/PMC480898/ /pubmed/15199145 http://dx.doi.org/10.1128/MCB.24.13.5900-5913.2004 Text en Copyright © 2004, American Society for Microbiology
institution US National Library of Medicine
collection PubMed Central
language English
format Article
topic Cell Growth and Development
spellingShingle Cell Growth and Development
Razandi, Mahnaz
Pedram, Ali
Rosen, Eliot M.
Levin, Ellis R.
BRCA1 Inhibits Membrane Estrogen and Growth Factor Receptor Signaling to Cell Proliferation in Breast Cancer
description BRCA1 mutations and estrogen use are risk factors for the development of breast cancer. Recent work has identified estrogen receptors localized at the plasma membrane that signal to cell biology. We examined the impact of BRCA1 on membrane estrogen and growth factor receptor signaling to breast cancer cell proliferation. MCF-7 and ZR-75-1 cells showed a rapid and sustained activation of extracellular signal-related kinase (ERK) in response to estradiol (E2) that was substantially prevented by wild-type (wt) but not mutant BRCA1. The proliferation of MCF-7 cells induced by E2 was significantly inhibited by PD98059, a specific ERK inhibitor, or by dominant negative ERK2 expression and by expression of wt BRCA1 (but not mutant BRCA1). E2 induced the synthesis of cyclins D1 and B1, the activity of cyclin-dependent kinases Cdk4 and CDK1, and G(1)/S and G(2)/M cell cycle progression. The intact tumor suppressor inhibited all of these. wt BRCA1 also inhibited epidermal growth factor and insulin-like growth factor I-induced ERK and cell proliferation. The inhibition of ERK and cell proliferation by BRCA1 was prevented by phosphatase inhibitors and by interfering RNA knockdown of the ERK phosphatase, mitogen-activated kinase phosphatase 1. Our findings support a novel tumor suppressor function of BRCA1 that is relevant to breast cancer and identify a potential interactive risk factor for women with BRCA1 mutations.
author Razandi, Mahnaz
Pedram, Ali
Rosen, Eliot M.
Levin, Ellis R.
author_facet Razandi, Mahnaz
Pedram, Ali
Rosen, Eliot M.
Levin, Ellis R.
author_sort Razandi, Mahnaz
title BRCA1 Inhibits Membrane Estrogen and Growth Factor Receptor Signaling to Cell Proliferation in Breast Cancer
title_short BRCA1 Inhibits Membrane Estrogen and Growth Factor Receptor Signaling to Cell Proliferation in Breast Cancer
title_full BRCA1 Inhibits Membrane Estrogen and Growth Factor Receptor Signaling to Cell Proliferation in Breast Cancer
title_fullStr BRCA1 Inhibits Membrane Estrogen and Growth Factor Receptor Signaling to Cell Proliferation in Breast Cancer
title_full_unstemmed BRCA1 Inhibits Membrane Estrogen and Growth Factor Receptor Signaling to Cell Proliferation in Breast Cancer
title_sort brca1 inhibits membrane estrogen and growth factor receptor signaling to cell proliferation in breast cancer
publisher American Society for Microbiology
publisher_facet American Society for Microbiology
publishDate 2004
url https://ncbi.nlm.nih.gov/pmc/articles/PMC480898/
https://ncbi.nlm.nih.gov/pubmed/15199145
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1128/MCB.24.13.5900-5913.2004
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