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 these alterations in the cellular differentiation state are controlled by global alterations in chromatin which influence gene expression. Our specific goals were to test the susceptibility of Nkx3.1-null transit amplifying cells to transformation and tumorigenicity in vitro and in vivo in response to MYC and to examine the basis of the dysregulation of histone deacetylase enzymes and their functional consequences in Nkx3.1-null cells. To date, 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. These results indicate that Nkx3.1-deficient cells are sensitive to MYC-induced tumorigenicity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2010
- Accession Number
- ADA601748
Entities
People
- Sarki A. Abdulkadir
Organizations
- Vanderbilt University