Tumorigenic Potential of Transit-Amplifying Prostate Cells
Abstract
An understanding of the identity of the target cell for prostate cancer development is essential to the development of accurate diagnostic, prognostic and therapeutic approaches. We hypothesized that loss of the prostate tumor suppressor Nkx3.1 sensitizes cells to prostate tumorigenesis by arresting cells in a precursor transit amplifying state that is more susceptible to tumorigenesis by oncogenes such as c-MYC that can impart self-renewal potential. Further we hypothesize that Nkx3.1 function is regulated by the pioneer factor FoxA1. Our specific goals were to test the susceptibility of Nkx3.1-null transit amplifying cells to transformation and tumorigenicity in response to MYC and to test the hypothesis that FOXA1 is cofactor involved in the regulation of a subset of NKX3.1 target genes in prostate cells. We have established a tissue recombination system for prostate regeneration using primary mouse prostate cells. Using this system, we have obtained evidence that loss of Nkx3.1 cooperates with MYC expression in promoting prostate tumorigenesis in vivo. We have also obtained evidence that Nkx3.1 binding sites tend to co-occur with FOXA1 binding sites in prostate cells. Analysis of data genomic NKX3.1 and FOXA1 binding data from LNCaP cells indicated a significant overlap, with binding of these factors occurs near each other on the DNA.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2011
- Accession Number
- ADA601672
Entities
People
- Sarki A. Abdulkadir
Organizations
- Vanderbilt University