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Modulation of ERK and breast cancer cell growth by estrogen receptors (613.3)
Author(s) -
Rofelty Angela,
Schmitt John
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.613.3
Subject(s) - mapk/erk pathway , estrogen receptor , cell growth , cancer research , cancer cell , chemistry , estrogen , mcf 7 , phosphorylation , endocrinology , kinase , microbiology and biotechnology , medicine , breast cancer , biology , cancer , biochemistry , human breast
Estrogen Receptors participate in both genomic and non‐genomic signaling pathways that affect breast cancer cell growth and proliferation. The growth‐enhancing actions of estrogen (E2) in MCF‐7 breast cancer cells are mediated through Estrogen Receptor alpha (ERα), activating a kinase pathway involving CaM KK, CaM KI, and ERK. Conversely, overexpression of Estrogen Receptor beta (ERβ) has been shown to restrict the transcriptional activity of ERα and inhibit breast cancer cell growth. Our goal was to explore the roles of ERα and ERβ in ERK activation and cell growth in MCF‐7 and MDA‐MB‐231 breast cancer cells. E2 treatment of MCF‐7 cells led to a significant rise in phosphorylation of CaM KI and its downstream target, ERK, and this effect was blocked by pretreatment with the ERα antagonist MPP and siRNA directed against ERα. Inhibition of ERβ with its antagonist PHTPP did not reduce ERK activity following stimulation with E2. Interestingly, pretreatment of MCF‐7 cells with the ERβ agonist, FERb, prevented the activation of ERK by E2. Treatment of MCF‐7 cells with E2 stimulated an increase in cell growth that was blocked by pretreatment with MPP, but not by pretreatment with PHTPP. In both MCF‐7 and MDA‐MB‐231 cells, stimulation with FERb reduced cell growth slightly below control levels. Treatment of MDA‐MB‐231 cells with FERb rapidly increased ERK phosphorylation and this effect was blocked by pretreatment with PHTPP. Our data suggest ERβ differentially regulates ERK in MCF‐7 and MDA‐MB‐231 cells. While activation of ERβ inhibits the growth of both cell lines, ERβ prevents ERK phosphorylation in MCF‐7 cells, but enhances ERK phosphorylation in MDA‐MB‐231 cells. Grant Funding Source : Supported by M.J.Murdock Charitable Trust #2011267