Generation of stable reporter breast cancer cell lines for the identification of ER subtype selective ligands

Erin K. Shanle, John R Hawse, Wei Xu

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Estrogen signaling is mediated by two estrogen receptors (ERs), ERα and ERβ, which have unique roles in the regulation of breast cancer cell proliferation. ERα induces proliferation in response to estrogen and ERβ inhibits proliferation in breast cancer cells, suggesting that ERβ selective ligands may be beneficial for promoting the anti-proliferative action of ERβ. Subtype selective ligands can be identified using transcriptional assays, but cell lines in which ERα or ERβ are independently expressed are required. Of the available reporter cell lines, none have been generated in breast cancer cells to identify subtype selective ligands. Here we describe the generation of two isogenic breast cancer cell lines, Hs578T-ERαLuc and Hs578T-ERβLuc, with stable integration of an estrogen responsive luciferase reporter gene. Hs578T-ERαLuc and Hs578T-ERβLuc cell lines are highly sensitive to estrogenic chemicals and ER subtype selective ligands, providing a tool to characterize the transcriptional potency and subtype selectivity of estrogenic ligands in the context of breast cancer cells. In addition to measuring reporter activity, ERβ target gene expression and growth inhibitory effects of ERβ selective ligands can be determined as biological endpoints. The finding that activation of ERβ by estrogen or ERβ selective natural phytoestrogens inhibits the growth of Hs578T-ERβ cells implies therapeutic potential for ERβ selective ligands in breast cancer cells that express ERβ.

Original languageEnglish (US)
Pages (from-to)1940-1949
Number of pages10
JournalBiochemical Pharmacology
Volume82
Issue number12
DOIs
StatePublished - Dec 15 2011

Fingerprint

Estrogen Receptors
Cells
Breast Neoplasms
Ligands
Cell Line
Estrogens
Phytoestrogens
Cell proliferation
Growth
Luciferases
Reporter Genes
Gene expression
Assays

Keywords

  • Breast cancer
  • Estrogen receptors
  • Phytoestrogens
  • Subtype selectivity

ASJC Scopus subject areas

  • Pharmacology
  • Biochemistry

Cite this

Generation of stable reporter breast cancer cell lines for the identification of ER subtype selective ligands. / Shanle, Erin K.; Hawse, John R; Xu, Wei.

In: Biochemical Pharmacology, Vol. 82, No. 12, 15.12.2011, p. 1940-1949.

Research output: Contribution to journalArticle

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