Culig Z, Hobisch A, Hittmair A, Peterziel H, Radmayr C, Bartsch G, Cato A C, Klocker H
Department of Urology, University of Innsbruck, Austria.
Histol Histopathol. 1997 Jul;12(3):781-6.
Investigations on androgen signaling alterations in the late stages of prostate cancer revealed new molecular mechanisms that may be in part responsible for failure of endocrine therapy. Both primary and metastatic lesions from prostate cancer express androgen receptor protein. Amplification of androgen receptor gene occurs in a subset of prostate cancer patients. Several point mutations of androgen receptor gene have been described; they generate receptors which are functionally activated by androgens, other steroids, and even by antihormones. The frequency of androgen receptor mutations may be high in tumor metastases. Functional activity of androgen receptor is influenced by nonsteroidal factors, such as peptide growth factors and second messengers. Thus, prostate cancer cells adapt to low androgen environment by various mechanisms utilizing androgen receptor. Therefore, new strategies for switching off the androgen receptor are needed.
对前列腺癌晚期雄激素信号改变的研究揭示了新的分子机制，这些机制可能部分导致内分泌治疗失败。前列腺癌的原发性和转移性病变均表达雄激素受体蛋白。雄激素受体基因扩增发生在一部分前列腺癌患者中。已描述了雄激素受体基因的几种点突变；它们产生的受体可被雄激素、其他类固醇甚至抗激素功能性激活。雄激素受体突变在肿瘤转移中的频率可能很高。雄激素受体的功能活性受非甾体因素影响，如肽生长因子和第二信使。因此，前列腺癌细胞通过利用雄激素受体的各种机制适应低雄激素环境。因此，需要新的关闭雄激素受体的策略。
