Genetic and Epigenetic Silencing of the AS3 Proliferative Arrest Gene in Prostate Cancer
Abstract
Prostate cancer is the second leading cause of death among American men. The present proposal extends the molecular progress in prostate cancer into clinical practice by developing innovative markers. The current androgen ablation treatment is initially therapeutic, but most patients relapse. A novel androgen substitution approach uses androgens to promote terminal differentiation and arrest cancer. Markers of differentiation, however, are not known in the prostate. We discovered a novel gene, AS3 (new name APRIN), a marker of proliferative arrest and differentiation. We mapped the AS3 gene on chromosome 13 and we found that the loss of the gene correlates with a high incidence of prostate cancer. In many of the cancers genetic markers are not informative, raising the possibility that epigenetic mechanisms contribute to AS3 silencing. The objective of this proposal is to investigate the epigenetic mechanisms to assess AS3 gene silencing in prostate cancer. In the first year we established the technology to isolate cancer specific DNA and worked out the methylation specific PCR and sequencing techniques on the AS3 promoter. We generated the first data that methylation of the APRIN promoter is critical in the silencing of the gene and correlates with hormone resistance in the LNCaP-TJA prostate cancer cell line. These data have been confirmed by direct sequencing of the bisulfite-converted amplified promoter elements. In addition, these data identified methylation hot-spots in the promoter of the APRIN gene. Our results established a critical set of reagents and experience for the tasks of the second year.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2004
- Accession Number
- ADA427177
Entities
People
- Peter Geck
Organizations
- Tufts University