Accession Number:

ADA443071

Title:

Genetic and Epigenetic Silencing of the AS3 Proliferative rrest Gene in Prostate Cancer

Descriptive Note:

Annual rept. 1 Apr 2004-31 Mar 2005

Corporate Author:

TUFTS UNIV BOSTON MA

Personal Author(s):

Report Date:

2005-04-01

Pagination or Media Count:

17.0

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. In the second year we analyzed DNA methylation in the entire CpG island of the APRIN promoter. We identified the methylation map and discovered methylation hot spots. By using these data we analyzed APRIN promoter methylation in various prostate cancer samples and established preliminary correlations with histology.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE