Estrogen receptor α/β isoforms, but not βcx, modulate unique patterns of gene expression and cell proliferation in Hs578T cells

Frank J. Secreto, David G Monroe, Shamit Dutta, James N. Ingle, Thomas C. Spelsberg

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1125-1147
Number of pages23
JournalJournal of Cellular Biochemistry
Volume101
Issue number5
DOIs
StatePublished - Aug 1 2007

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Keywords

  • Breast cancer
  • Estrogen receptor
  • Gene expression
  • Microarrays
  • Proliferation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Estrogen receptor α/β isoforms, but not βcx, modulate unique patterns of gene expression and cell proliferation in Hs578T cells. / Secreto, Frank J.; Monroe, David G; Dutta, Shamit; Ingle, James N.; Spelsberg, Thomas C.

In: Journal of Cellular Biochemistry, Vol. 101, No. 5, 01.08.2007, p. 1125-1147.

Research output: Contribution to journalArticle