SOX9 mediates the retinoic acid-induced HES-1 gene expression in human breast cancer cells

Patrick Müller, Justin D. Crofts, Ben S. Newman, Laura C. Bridgewater, Chin Yo Lin, Jan Åke Gustafsson, Anders Ström

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

We have previously shown that the anti-proliferative effect of retinoic acid in human breast cancer cell line MCF-7 is dependent on HES-1 expression. Here we show that retinoic acid induces HES-1 expression via upregulation of transcription factor SOX9. By expressing a dominant negative form of SOX9, disrupting endogenous SOX9 activity, the retinoic acid-induced HES-1 mRNA expression was inhibited. We found an enhancer regulating HES-1 expression: two SOX9 binding sites upstream of the HES-1 gene that were capable of binding SOX9 in vitro. By performing chromatin immunoprecipitation, we showed that SOX9 binding to the HES-1 enhancer was induced by retinoic acid in vivo. In reporter assays, transfection of a SOX9 expression plasmid increased the activity of the HES-1 enhancer. The enhancer responded to retinoic acid; furthermore, the expression of a dominant negative SOX9 abolished this response. Taken together, we present here a novel transcriptional mechanism in regulating hormonedependent cancer cell proliferation.

Original languageEnglish (US)
Pages (from-to)317-326
Number of pages10
JournalBreast Cancer Research and Treatment
Volume120
Issue number2
DOIs
StatePublished - Apr 2010

Keywords

  • Atra
  • HES-1
  • SOX9 proliferation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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