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01-04-2010 | Preclinical study

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

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

Published in: Breast Cancer Research and Treatment | Issue 2/2010

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 hormone-dependent cancer cell proliferation.

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Title: SOX9 mediates the retinoic acid-induced HES-1 gene expression in human breast cancer cells
Authors: Patrick Müller
Justin D. Crofts
Ben S. Newman
Laura C. Bridgewater
Chin-Yo Lin
Jan-Åke Gustafsson
Anders Ström
Publication date: 01-04-2010
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 2/2010
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-009-0381-6

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