Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Biochem Biophys Res Commun. 2008 Sep 19;374(2):388-93. doi: 10.1016/j.bbrc.2008.07.056. Epub 2008 Jul 18.

FOXP1 is an androgen-responsive transcription factor that negatively regulates androgen receptor signaling in prostate cancer cells.

Author information

  • 1Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

Abstract

Androgen and androgen receptor (AR) play important roles in the formation and the progression of prostate cancer. AR activates its target genes by recruiting various coregulators and transcriptional factors. Here we show that the FOXP1 forkhead transcription factor is a novel androgen-regulated gene. By sequencing DNA fragments obtained from chromatin immunoprecipitation (ChIP), a bona-fide AR binding site (ARBS) is identified in an intron region of FOXP1 gene. FOXP1 can be induced by androgen in hormone-sensitive prostate cancer LNCaP cells at both mRNA and protein levels. In particular, a smaller FOXP1 variant, FOXP1D, is upregulated in response to androgen. Notably, we demonstrate that FOXP1 directly interacts with AR and negatively regulates AR signaling ligand-dependently, as exemplified by the transcriptional repression of PSA gene regulated by androgen-dependent FOXP1 recruitment on its enhancer region. We show that several other forkhead transcription factors are also androgen-responsive in LNCaP cells. Our study provides a new insight to the function of forkhead transcription factors that modulates AR signaling as an androgen-regulated transcriptional factor, which would contribute to the tumorigenesis of prostate cancer.

PMID:
18640093
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk