The Role of Androgen Receptor-Target Genes in Racial Disparity of Prostate Cancer
Abstract
AR mediates transcriptional activation through a series of events including ligand binding, binding to cognate androgen response elements (AREs) and interaction with various coactivators, resulting in transcriptional initiation of AR target genes by the general transcriptional machinery 1 (Fig.2). The mechanism responsible for the switch of AR mediated growth promotion and inhibition could be due to the different set of AR target genes activated. Recent efforts in identifying AR target genes in prostatic cell lines and human cancer using DNA microarrays have resulted in the identification of several AR target genes 2-7. It is of particular interest of this proposal to determine whether any of these are also expressed in prostate stromal cells and whether their expression contribute to racial disparity of prostate cancer. In an effort to understand their role in prostate cancer proliferation and differentiation, we have also identified several genes as AR target genes including cellular caspase-8 (FLICE)-like inhibitory protein, c-FLIP 8 by deletional, mutational and chromatin immunoprecipitation analysis of the promoter region of the gene of interest. c-FLIP is an androgen receptor target gene, affecting survival and apoptosis of prostate cells 8. LNCaP cells infected with a retrovirus harboring c-FLIP lead to increased levels of c-FLIP protein and accelerated the progression to androgen independence. In addition to its increased expression in human prostate cancer cells, we found that there are an increased number of c-FLIP positive stromal cells surrounding prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2007
- Accession Number
- ADA502368
Entities
People
- Patrice S. Pearce
Organizations
- New York University