雄激素受体信号转导途径及其在前列腺癌发展中的作用

前列腺癌是西方男性发病率最高的癌症之一,在采用雄激素阻断疗法后,大部分患者的病情可得到控制,但经过一段时间又会转变为雄激素非依赖型前列腺癌。雄激素受体(AR)在前列腺细胞中扮演重要的角色,它可调节大量基因的表达。在前列腺癌由雄激素依赖型向雄激素非依赖型的转变过程中,AR及其信号途径通过多种方式发挥作用,AR基因的扩增、AR的突变,以及与共激活子之间作用的改变都可能使细胞获得雄激素非依赖型的生长能力。此外,AR还受到多肽生长因子和细胞因子等的调节,表现激素非依赖型的转录激活活性。AR在前列腺癌中作用的阐明对前列腺癌的诊断与治疗有着重大的意义。

Androgen Receptor Signaling Pathway and its Function in Prostate Cancer Progression

Prostate cancer is one of the most prevalent cancers in males in the western countries. The standard therapy is to block the actions of androgens by castration or antiandrogens. However after some time of the androgen ablation therapy some tumors may lose response to androgens and become androgen-independent. The androgen receptor AR plays a key role in both normal prostate tissue and the progression of prostate cancer. Amplification or mutation of the AR as well as alterations in interactions with coactivators may offer the cancer cells the ability to grow despite androgen ablation. Also AR is regulated by peptide growth factors and cytokines in a hormone independent manner. Therefore to clarify the function of AR may have significant diagnostic and therapeutic meanings.