Accession Number : ADA590408


Title :   The Role of ERG and CXCR4 in Prostate Cancer Progression


Descriptive Note : Final rept. 11 May 2009-10 May 2013


Corporate Author : WAYNE STATE UNIV DETROIT MI


Personal Author(s) : Chinni, Sreenivasa R


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a590408.pdf


Report Date : Jun 2013


Pagination or Media Count : 88


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 CXCL12/CXCR4 axis transactivates EGFR family members in PC cells and functions in PC progression to enhance invasion and metastasis. To address the mechanism of CXCL12/CXCR4 transactivation of EGFR family members, we evaluated the location of transactivation at cellular, cell surface and lipid raft microdomains. To determine the impact of CXCL12/CXCR4 activation on initial colonization of bone tissue, we targeted CXCL12/CXCR4 axis with a small molecule CXCR4 inhibitor AMD3100. Results of the current study show that (a) CXCL12/CXCR4 transactivation of EGFR members is confined to lipid raft membrane microdomains and (b) targeting CXCL12/CXCR4 axis with AMD3100 resulted in delayed growth of bone tumors. These findings demonstrate CXCL12/CXCR4 transactivation of EGFR members in lipid raft membrane microdomains contribute to initial colonization and growth of PC cells to bone metastatic site.


Descriptors :   *ANDROGENS , *CELLS(BIOLOGY) , *GENE EXPRESSION , *PROSTATE CANCER , BONES , LIGANDS , LIPIDS , METASTASIS , MOLECULES , NEOPLASMS , TISSUES(BIOLOGY)


Subject Categories : Biochemistry
      Genetic Engineering and Molecular Biology
      Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE