The Role of Mutant p53 in Progression of Prostate Cancer
Abstract
p53 mutation is frequently found in advanced prostate cancers (CaP) such as androgen independent CaP which suggests that mutant p53 may have a role in the progression of CaP. By generating of a series of prostate cancer cell lines in which wild-type or mutant p53 is knocked down and (or) various mutant p53 are simultaneously expressed we found that knock- down of wild-type p53 confers CaP cells resistance to DNA damage-induced apoptosis. In addition knock-down of mutant p53 renders CaP cells more sensitive to DNA damage-induced apoptosis. However CaP cell death upon deprivation of androgen is independent of wild-type p53. Moreover knock-down of mutant p53 is unable to convert the androgen-independent CaP cells to androgen-dependent ones. Interestingly re-introduction of mutant p53 into wild-type p53 knock-down CaP cells further increases their resistance to DNA-damage induced apoptosis. More importantly re-introduction of mutant p53 into wild-type p53 knock-down CaP cells promotes their androgen-independent growth. Finally we found that p53 activation upon DNA damage is impaired by deprivation of androgen.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2005
- Accession Number
- ADA484103
Entities
People
- Gang Liu
Organizations
- University of Alabama