MT 2A Phosphorylation by PKC Mu/PKD Influences Chemosensitivity to Cisplatin in Prostate Cancer; Annual rept. 1 Nov 2006-31 Oct 2007

摘要

The metallothioneins (MT) are a family of small molecular weight trace metal and free radical scavenging proteins well established to play a role in resistance to chemotherapy and radiation in human cancer. MT gene expression is up regulated in response to the presence of heavy metal ions such as zinc. The activation of MT gene expression in response to zinc treatment in LNCaP and C4-2 prostate cancer (PC) cells was shown by western blotting and DNA microarray analysis. Chemotherapy and radiation sensitivity assays of cells following treatment with cisplatin or radiation were performed in the presence or absence of 150 micron M ZnSO4 and cell viability measured after 72 hours by MTS viability clonogenic and flow cytometry assays. Increasing concentrations of ZnSO4 up regulated MT expression in a dose dependent manner. Microarray analysis demonstrated specific increase in MT expression. Cells treated with zinc demonstrated a significantly decreased sensitivity to cisplatin compared to controls.