We are interested in the possibility of a new prostate cancer therapy that would control tumor malignancy via induction of terminal cell differentiation. We previously reported that 12-O-tetra-decanoylphorbol-13-acetate (TPA) induces differentiation into cells with characteristics of microglia and decreases the malignant characteristics of human prostatic cancer TSU-Pr1 cells. To investigate the mechanism underlying differentiation of TSU-Pr1 cells, we attempted to identify genes expressed during differentiation using differential display. We identified four genes expressed differentially after TPA treatment. Levels of expression of two genes, human flavoprotein subunit of complex II and JKTBP, were downregulated by TPA, and expression of two genes, human golgin p245 and bcl-xL, was upregulated. Moreover, we found that the changes in expression of flavo-protein, JKTBP and bcl-xL induced by TPA were blocked by treatment with protein kinase C (PKC) or mitogen-activated protein (MAP) kinase inhibitors that prevent TPA-induced differentiation of TSU-Pr1 cells. These results suggest that the differential expression of these genes is associated with TPA-induced differentiation of TSU-Pr1 cells. We expect that understanding the roles of these genes during differentiation will provide for new approaches and therapeutic targets for treatment of prostate cancer.

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