From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Sat, Apr 12, 2008 at 8:54 PM
Subject: Estrogen-mediated downregulation of CD24 in breast cancer cells.
To: mesothelioma77@gmail.com
[1]Int J Cancer. 2008 Apr 10;
Kaipparettu BA, Malik S, Konduri SD, Liu W, Rokavec M, van der Kuip H, Hoppe R, Hammerich-Hille S, Fritz P, Schroth W, Abele I, Das GM, Oesterreich S, Brauch H
We have previously reported on the relevance of the prevalence of CD44(+)/CD24(-/low) cells in primary breast tumors. To study regulation of CD24, we queried a number of publicly available expression array studies in breast cancer cells and found that CD24 was downregulated upon estrogen treatment. We confirmed this estrogen-mediated repression of CD24 mRNA by quantitative real-time PCR in MCF7, T47D and ZR75-1 cells. Repression was also seen at the protein level as measured by flow cytometry. CD24 was not downregulated in the ERalpha negative MDA-MB-231 cells suggesting that ERalpha was necessary. This was further confirmed by ERalpha silencing in MCF7 cells resulting in increased CD24 levels and by reintroduction of ERalpha into C4-12 cells resulting in decreased CD24 levels. Estrogen treatment did not alter half-life of CD24 mRNA and new protein synthesis was not essential for repression, suggesting a primary transcriptional effect. Histone deacetylase inhibition by Trichostatin A completely abolished the repression, but decrease of the ERalpha corepressors NCoR, LCoR, RIP140, silencing mediator of retinoid and thyroid hormone receptors, SAFB1 and SAFB2 by siRNA or overexpression of SAFB2, NCoR and silencing mediator of retinoid and thyroid hormone receptors had no effect. In silico promoter analyses led to the identification of two estrogen responsive elements in the CD24 promoter, one of which was able to bind ERalpha as shown by electrophoretic mobility shift assay and chromatin immunoprecipitation assay. Together, our results show that CD24 is repressed by estrogen and that this repression is a direct transcriptional effect depending on ERalpha and histone deacetylases. (c) 2008 Wiley-Liss, Inc.
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Source: http://www.hubmed.org/display.cgi?uids=18404683
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