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

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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See also All-Trans-Retinoic Acid (ATRA - analogues and/or derivatives).