The Double-Edged Sword of Prostate Cancer: 14-3-3(sigma)
Abstract
In the first year of study, we tested the hypothesis that advanced and hormone refractory prostate cancers may have increased 14-3-3sigma expression, which in turn may contribute to drug resistance in advanced and hormone-refractory prostate cancers. We found that, indeed, the expression level of 14-3-3sigma in androgen-independent prostate cancer cell lines DU145 and PC3 are much higher than that in the androgen-dependent cell line LNCaP and that the androgen-independent cells are more resistant to mitoxantrone and Adriamycin than the androgen-dependent cells. Down-regulating 14-3-3sigma expression in the androgen-independent cell line DU145 by small interference RNA significantly sensitized these cells to mitoxantrone and Adriamycin by causing failure in maintaining G2/M checkpoint and increasing apoptosis. We also showed that 14-3-3sigma deficiency caused nuclear localization of Cdc2 and dephosphorylation of the Tyr15 residue upon DNA damage. Based on these studies, we propose that therapeutic intervention targeting 14-3-3sigma may prove to be useful for sensitizing hormone-refractory prostate cancers to chemotherapy by both G2/M checkpoint abrogation and enhancing apoptotic cell death.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2005
- Accession Number
- ADA447234
Entities
People
- Jian-Ting Zhang
Organizations
- Indiana University