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

Breast Cancer Res Treat. 2010 Apr;120(2):317-26.
Müller P, Crofts JD, Newman BS, Bridgewater LC, Lin CY, Gustafsson JA, Ström A.
Breast Cancer Res Treat. 2010 Apr;120(2):317-26.
L'effetto anti-proliferativo dell' acido retinoico nella linea cellulare del carcinoma mammario umano MCF-7 è dipendente dall'espressione del gene HES-1 attraverso la sovra-regolazione del fattore di trascrizione SOX9.
RA/carcinoma mammario.

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.