Explication of mechanism in hormone refractory status in prostate cancer, Analysis of androgen receptor and related factors

在此期间，我能够分析的结果如下：前列腺癌患者的2号染色体上至少存在一个座位的杂合性缺失(Loss of Heterozygity，LOH)。2p上的杂合性缺失在癌症死亡病例中的发生率高于器官受限和区域性疾病。这些结果表明，2号染色体上可能的肿瘤抑制基因的失活可能在日本PCA患者的进展中起重要作用。I已经证明，在激素不敏感的PCa中，血清IL-4水平增加，IL-4通过激活ARNTD增强人LNCaP细胞中PSA报告基因的活性。这些结果表明，AR可以被细胞因子激活，这一机制可能在前列腺癌患者接受雄激素治疗后从雄激素依赖向雄激素非依赖性转变过程中发挥重要作用。血清嗜铬粒素A和与神经内分泌分化相关的NSE被报道为前列腺癌患者激素治疗的预后因素。IL-10还以与IL-6、IL-4相同的方式激活前列腺癌细胞中的雄激素受体。我利用双向凝胶电泳法对前列腺癌患者激素治疗后获得的血清蛋白进行了分析。我已经发表了上述研究成果的一部分，并在本报告中列出了主要论文。

The results which I was able to analyze in this period were as follows.Loss of heterozygosity (LOH) were present at least one locus on chromosome 2 of prostate cancer patients. LOH on 2p was observed more frequently in cancer death cases than in organ confined and regional diseases. These results suggest that inactivation of putative tumor suppressor genes on chromosome 2 that may play an important role in the progression of Japanese patients with PCa.I have demonstrated that serum levels of IL-4 are increased in hormone refractory PCa and IL-4 enhanced PSA reporter gene activity by the activation of ARNTD in human LNCaP cells. These results suggest that the AR can be activated by cytokines and this mechanism may play an important role in the transition from androgen-dependent to androgen-independent prostate cancer after patients receive androgen ablation therapy.Serum chromogranin A and NSE related to neuroendocrine differentiation reported it as prognostic factor of hormonotherapy for prostate cancer patients.I analyzed the influence that IL -10 gave to an androgen receptor. IL -10 also activated androgen receptor in in the same way as IL -6, and IL -4 in prostate cancer cells.I analyzed serum proteins obtained from prostatic cancer patients treating by the hormone therapy by means of 2 dimensions of electrophoresis.I already published one part of above-mentioned results of research, and the main papers were shown in this report.From this study, I was able to analyze about androgen refractory molecular biologic mechanism of hormone refractory prostate from the various aspects.