Examination of the Role of DNA Methylation Changes in Prostate Cancer Using the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) Model
Abstract
The TRansgenic Adenocarcinoma of Mouse Prostate (TRAMP) model provides an excellent system to study disruption of the DNA methylation process in prostate cancer. To date, several key conclusions can be made from this research. First, analysis of methylation patterns in TRAMP revealed a small number of hypermethylation events in early stage lesions, with a great increase in late stage tumors. Furthermore, late stage tumors, androgen independent tumors and metastases each display numerous and tumor type specific hypermethylation events. Secondly, a large proportion of these hypermethylated genes, including p19/ARF and p16INK4a, display downstream hypermethylation correlating with robust overexpression. In addition, p16 and p19 overexpression, but not downstream hypermethylation, occurs in early stage prostatic lesions in TRAMP, suggesting that overexpression may be the initiating event and pharmacological reversal of downstream hypermethylation in TRAMP cell lines led to decreased expression of p19 and p16, indicating that downstream hypermethylation contributes to the maintenance of increased gene expression. Overall these data indicate that locus specific hypermethylation is selected for upon tumor progression and treatment with hypomethylating agents may inactivate oncogenes whose expression is maintained by downstream hypermethylation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2008
- Accession Number
- ADA483413
Entities
People
- Shannon R. Morey
Organizations
- Roswell Park Comprehensive Cancer Center