Accession Number:

ADA592440

Title:

Role of p53 in cdk Inhibitor VMY-1-103-induced Apoptosis in Prostate Cancer

Descriptive Note:

Annual rept. 22 Aug 2011-21 Aug 2013

Corporate Author:

GEORGETOWN UNIV WASHINGTON DC

Personal Author(s):

Report Date:

2013-11-01

Pagination or Media Count:

15.0

Abstract:

Cyclin-dependent kinase inhibitor VMY-1-103 induces a G2M cell cycle arrest and apoptosis in prostate cancer cell lines. Cancer cell lines, including prostate cancer, show a differential sensitivity to VMY-1-103 that correlates with p53 status. In addition, VMY-1-103 sensitivity increases in cancer cell lines as compared with normal cell lines, regardless of p53 status. Knockdown experiments in LNCaP cells show a reduced sensitivity to VMY-1-103 by resulting in a decreased cell death and this result can be rescued by the addition of wild-type p53. Transient transfections of wild-type p53 into p53-null PC-3 cells resulted in increased cell death upon VMY treatment. Furthermore, PRIMA-1 pre-treatment restored p53 activity in p53-mutant DU145 cells and sensitized them to VMY-mediated cell death. As compared with other solid tumors, only a small percentage of prostate cancer cases contain p53 mutations. Therapeutically, this is important as a majority of prostate cancer patients could benefit from VMY.

Subject Categories:

  • Biology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE