Accession Number:

ADA609541

Title:

The Role of ERG and CXCR4 in Prostate Cancer Progression

Descriptive Note:

Annual rept. 11 May 2009-10 May 2010

Corporate Author:

WAYNE STATE UNIV DETROIT MI

Personal Author(s):

Report Date:

2010-06-01

Pagination or Media Count:

20.0

Abstract:

TMPRSS2-ERG fusion transcripts have been shown to be expressed in a majority of prostate cancer PC patients due to chromosomal translocations or deletions involving the TMPRSS2 gene promoter and the ERG gene coding sequence. These alterations cause androgen dependent ERG transcription factor expression in PC patients. We and others have shown that chemokine receptor CXCR4 expression is upregulated in PC tumor cells and its ligand, CXCL12, is expressed in bone stromal cells. The CXCL12CXCR4 axis functions in PC progression to enhance invasion and metastasis. To address the regulation of CXCR4 expression, we identified several putative ERG consensus binding sites in the promoter region of CXCR4. We hypothesized that androgen dependent regulation of the ERG transcription factor could induce CXCR4 expression in PC cells. Results of the current study show that a selective ERG binding elements in CXCR4 promoter interact with nuclear proteins from TMPRSS2-ERG fusion positive VCaP cells b synthetic androgen R1881 upregulates CXCR4 in TMPRSS2- ERG fusion positive VCaP cells c R1881 activated TMPRSS2-ERG expression functionally activates CXCR4 in VCaP cells. These findings provide a link between TMPRSS2-ERG translocations and enhanced metastasis of tumor cells via CXCR4 function in PC cells.

Subject Categories:

  • Biology
  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE