The Role of Mutant p53 in Progression of Prostate Cancer
Abstract
The 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. The authors generated a series of prostate cancer cell lines in which wild-type or mutant p53 is knocked down and/or various mutant p53 are simultaneously inducibly expressed. They found that knock-down of wild-type p53 gives CaP cells resistance to DNA damage-induced apoptosis, whereas knock-down of mutant p53 renders CaP cells more sensitive to DNA damage-induced apoptosis. They also found that CaP cell death upon deprivation of androgen is independent of wild-type p53, and that 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. Moreover, re-introduction of mutant p53 into wild-type p53 knock-down CaP cells promotes their androgen-independent growth. Finally, they found that p53 activation upon DNA damage is impaired by androgen deprivation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2004
- Accession Number
- ADA447626
Entities
People
- Gang Liu
Organizations
- University of Alabama