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Estrogen receptor α/β isoforms, but not βcx, modulate unique patterns of gene expression and cell proliferation in Hs578T cells
Author(s) -
Secreto Frank J.,
Monroe David G.,
Dutta Shamit,
Ingle James N.,
Spelsberg Thomas C.
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21205
Subject(s) - gene isoform , estrogen receptor , microbiology and biotechnology , estrogen related receptor alpha , gene expression , gene , cell growth , biology , receptor , estrogen , estrogen receptor alpha , estrogen receptor beta , genetics , cancer , breast cancer
The actions of 17β‐estradiol (E2) and selective estrogen receptor modulators (SERMs) have been extensively investigated regarding their ability to act through estrogen receptor‐α (ERα) to perturb estrogen receptor positive (ER+) breast cancer (BC) growth. However, many BCs also express ERβ, along with multiple estrogen receptor (ER) splice variants such as ERβcx, an ERβ splice variant incapable of binding ligand. To gain a more comprehensive understanding of ER action in BC cells, we stably expressed ERα, ERβ, or ERβcx under doxycycline (Dox) control in Hs578T cells. Microarrays performed on E2 or 4OH‐tamoxifen (4HT) treated Hs578T ERα and ERβ cells revealed distinct ligand and receptor‐dependent patterns of gene regulation, while the induction of ERβcx did not alter gene expression patterns. E2 stimulation of Hs578T ERβ cells resulted in a 27% decrease in cellular proliferation, however, no significant change in proliferation was observed following the exposure of Hs578T ERα or ERβ cells to 4HT. Expression of ERβcx in Hs578T cells did not effect cellular proliferation. Flow cytometry assays revealed a 50% decrease in E2‐stimulated Hs578T ERβ cells entering S‐phase, along with a 17% increase in G0/G1 cell‐cycle arrest. We demonstrate here that ERα and ERβ regulate unique gene expression patterns in Hs578T cells, and such regulation likely is responsible for the observed isoform‐specific changes in cell proliferation. Hs578T ER expressing cell‐lines provide a unique BC model system, permitting the comparison of ERα, ERβ, and ERβcx actions in the same cell‐line. J. Cell. Biochem. 101:1125–1147, 2007. © 2007 Wiley‐Liss, Inc.