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

我们已经尝试建立一种新的前列腺癌治疗方法，通过控制肿瘤细胞的恶性循环，通过体外终端细胞差异的定义。对人类前列腺癌细胞线差异定义的各种试剂的影响（LNCaP，TSU-Pr 1）进行了审查。Combination of prostaglandin E-D22-D2 and papaverine effectively induces differentiation of LNCaP cells to the cells with partly neuronal？teristics。Phorbol ester，12-O-四-十二烷基phorbol-13-acetate（TPA），TSU-Pr 1细胞的差异化与微胶质细胞的特征学有关。对这些受体的治疗导致了在软琼脂上的退化和对基质的感染性活动的抑制。这些结果建议降低了该地区LNCaP和TSU-Pr 1细胞的恶性循环。我们下一次对不同基因表达的研究性改变，在受诱导的差异化过程中。肿瘤素的表达，如C-myc和Bcl-2在这些不同的细胞中受到了抑制。TPA治疗诱导TSU-Pr 1细胞中CDK抑制剂p21蛋白表达。我们还发现，该指数是通过PKC和MAPK信号通路介导的。Moreover，我们已经确定了一些基因，其中TSU-Pr 1细胞在使用不同显示技术时表现出了不同的诱导差异。在这项研究中，我们展示了人类前列腺癌细胞可以通过治疗与适当的试剂盒一起被诱导的差异化来抑制残疾。我们还建议，对不同基因表达的改变与受诱导的差异有关。

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.