Change of characterization of human prostate cancer cells to neuronal cells by differentiation induction.

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We have been attempting to establish a new method of prostate cancer therapy by controlling the malignancy of tumor cells through the induction of terminal cell differentiation in vitro. The effects of various reagents on the induction of differentiation of the human prostate cancer cell lines (LNCaP, TSU-Pr1) were examined. Combination of prostaglandin EィイD22ィエD2 and papaverine effectively induces differentiation of LNCaP cells to the cells with partly neuronal characteristics. The phorbol ester, 12-O-tetra-decanoylphorbol-13-acetate (TPA), induces differentiation of TSU-Pr1 cells into the cells with characteristics of microglia. Treatment with these reagents caused decrease in colony formation on soft agar and suppression of invasive activity against matrigel. These results suggest that the regents reduced the malignancy of LNCaP and TSU-Pr1 cells. We next investigated alteration of expression of various genes during the induced differentiation. The expression of oncogenes such as c-myc and Bcl-2 was suppressed in these differentiated cells. Treatment with TPA induced the expression of CDK inhibitor p21 protein in TSU-Pr1 cells. We also detected that the induction is mediated through PKC and MAPK signal pathway. Moreover, we identified some genes that are differentially expressed during induced differentiation of TSU-Pr1 cells using differential display technique. In this study, we showed that human prostate cancer cells can be induced differentiation accompanied with decrease of malignancy by treatment with appropriate reagents. We also suggested that the alteration of expression of various genes is associated with the induced differentiation.