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

通过分化诱导将人前列腺癌细胞的特征改变为神经元细胞。

基本信息

批准号：
10672060
负责人：
TAKEDA Ken
金额：
$ 1.79万
依托单位：
Science University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10672060/
关键词：
Prostate Cancer differentiation LNCaP TSU-Pr1 Neuronal Cell Microglia LNCap 遺伝子発現

项目摘要

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.

我们一直试图通过体外诱导终末细胞分化来控制肿瘤细胞的恶性程度，从而建立一种治疗前列腺癌的新方法。检查各种试剂对人前列腺癌细胞系（LNCaP、TSU-Pr 1）的分化诱导的效果。前列腺素E β D22 β D2和罂粟碱的组合有效地诱导LNCaP细胞分化为具有部分神经元特征的细胞。佛波醇酯12-O-十四酰基佛波醇-13-乙酸酯（TPA）可诱导TSU-Pr 1细胞分化为具有小胶质细胞特征的细胞。用这些试剂处理引起软琼脂上的集落形成减少和对基质胶的侵袭活性抑制。这些结果表明，试剂降低LNCaP和TSU-Pr 1细胞的恶性度。接下来，我们研究了诱导分化过程中各种基因表达的变化。在这些分化的细胞中，癌基因如c-myc和Bcl-2的表达被抑制。TPA诱导TSU-Pr 1细胞表达CDK抑制剂p21蛋白。我们还检测到这种诱导是通过PKC和MAPK信号通路介导的。此外，我们还利用差异显示技术鉴定了TSU-Pr 1细胞诱导分化过程中的一些差异表达基因。在本研究中，我们发现，通过用适当的试剂处理，可以诱导人前列腺癌细胞分化，同时降低恶性程度。我们还认为，各种基因表达的改变与诱导分化有关。