Identification of estrogen-induced genes downregulated by AhR agonists in MCF-7 breast cancer cells using suppression subtractive hybridization

I. Chen, T. Hsieh, T. Thomas, S. Safe

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Aryl hydrocarbon receptor (AhR) agonists inhibit 17β-estradiol (E2) induced growth of MCF-7 human breast cancer cells in vitro and rodent mammary tumor growth in vivo. Genes associated with inhibitory AhR-estrogen receptor (ER) crosstalk were investigated in MCF-7 human breast cancer cells using poly(A)+RNA from cells treated with either 1 nM E2 (target) or E2 plus 1 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (reference) or 25 μM diindolylmethane (DIM) as AhR agonists in MCF-7 cells. Suppression subtractive hybridization (SSH) was subsequently used to identify 33 genes with sequence homology to known human genes that are induced by E2 and inhibited by AhR agonists in MCF-7 cells; two unknown genes were also identified. Many of these genes are involved in cell proliferation and these include cell cycle regulators (cdc28/cdc2-associated protein), nucleotide synthases (thymidylate synthase), early intermediate genes (early growth response α, EGRα) and other proteins involved in signaling pathways (calmodulin, ATP synthase α subunit). Thus SSH has identified a diverse spectrum of new genes that are affected by inhibitory AhR-ER crosstalk and among this group are a subset of genes that may be critical for the in vivo antitumorigenic effects of AhR agonists.

Original languageEnglish (US)
Pages (from-to)207-214
Number of pages8
JournalGene
Volume262
Issue number1-2
DOIs
StatePublished - Jan 10 2001
Externally publishedYes

Keywords

  • Antiestrogens
  • Gene expression

ASJC Scopus subject areas

  • Genetics

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