SOX9 mediates the retinoic acid-induced HES-1 gene expression in human breast cancer cells.
Breast Cancer Res Treat
; 120(2): 317-26, 2010 Apr.
Article
in En
| MEDLINE
| ID: mdl-19322650
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Breast Neoplasms
/
Gene Expression Regulation, Neoplastic
/
Homeodomain Proteins
/
Basic Helix-Loop-Helix Transcription Factors
/
SOX9 Transcription Factor
Limits:
Female
/
Humans
Language:
En
Journal:
Breast Cancer Res Treat
Year:
2010
Document type:
Article
Affiliation country:
Sweden