Guo Zhiyong, Dai Bojie, Jiang Tianyun, Xu Kexin, Xie Yingqiu, Kim Oekyung, Nesheiwat Issa, Kong Xiangtian, Melamed Jonathan, Handratta Venkatesh D, Njar Vincent C O, Brodie Angela M H, Yu Li-Rong, Veenstra Timothy D, Chen Hegang, Qiu Yun
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Cancer Cell. 2006 Oct;10(4):309-19. doi: 10.1016/j.ccr.2006.08.021.
The androgen receptor (AR) is essential for the growth of prostate cancer cells. Here, we report that tyrosine phosphorylation of AR is induced by growth factors and elevated in hormone-refractory prostate tumors. Mutation of the major tyrosine phosphorylation site in AR significantly inhibits the growth of prostate cancer cells under androgen-depleted conditions. The Src tyrosine kinase appears to be responsible for phosphorylating AR, and there is a positive correlation of AR tyrosine phosphorylation with Src tyrosine kinase activity in human prostate tumors. Our data collectively suggest that growth factors and their downstream tyrosine kinases, which are elevated during hormone-ablation therapy, can induce tyrosine phosphorylation of AR and such modification may be important for prostate tumor growth under androgen-depleted conditions.
雄激素受体（AR）对于前列腺癌细胞的生长至关重要。在此，我们报告AR的酪氨酸磷酸化由生长因子诱导，并在激素难治性前列腺肿瘤中升高。AR中主要酪氨酸磷酸化位点的突变在雄激素缺乏条件下显著抑制前列腺癌细胞的生长。Src酪氨酸激酶似乎负责AR的磷酸化，并且在人类前列腺肿瘤中AR酪氨酸磷酸化与Src酪氨酸激酶活性呈正相关。我们的数据共同表明，在激素消融治疗期间升高的生长因子及其下游酪氨酸激酶可诱导AR的酪氨酸磷酸化，并且这种修饰对于雄激素缺乏条件下的前列腺肿瘤生长可能很重要。
