Accession Number:

ADA495664

Title:

MT 2A Phosphorylation by PKC Mu/PKD Influences Chemosensitivity to Cisplatin in Prostate Cancer

Descriptive Note:

Final rept. 1 Nov 2004-31 Oct 2008

Corporate Author:

MASSACHUSETTS UNIV MEDICAL SCHOOL WORCESTER

Personal Author(s):

Report Date:

2008-11-01

Pagination or Media Count:

32.0

Abstract:

We showed that zinc treatment induced MT expression in LNCaP and C4-2 PCa cells as determined by Western blotting and DNA microarray analysis. Chemotherapy and radiation sensitivity assays of cells after treatment with cisplatin or radiation were performed in the presence, or absence, of 150 microM ZnSO4, and cell viability was measured after 72 hours by MTS viability and clonogenic and flow cytometry assays. The experiments were repeated three times and the data analyzed. We found that increasing concentrations of ZnSO4 upregulated MT expression in a dose-dependent manner. Microarray analysis demonstrated a specific increase in MT expression. Cells treated with zinc demonstrated a significantly decreased sensitivity to cisplatin and radiotherapy compared with controls P 0.05. Our data have confirmed that treatment of PCa with zinc causes an increase in MT expression, which is significantly associated with resistance to cisplatin chemotherapy and radiotherapy in prostate cancer. Therapeutic targeting of MT may therefore provide a means to overcome resistance to radiotherapy and cisplatin chemotherapy in prostate cancer.

Subject Categories:

  • Medicine and Medical Research
  • Radiobiology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE