Regulation of androgen receptor activity by tyrosine phosphorylation
Regulation of androgen receptor activity by tyrosine phosphorylation
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DOI：
10.1016/j.ccr.2006.08.021
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发表时间：
2006-10-01
期刊：
影响因子：
50.3
通讯作者：
Qiu, Yun
中科院分区：
文献类型：
--
作者：
Guo, Zhiyong;Dai, Bojie;Qiu, Yun
雄激素受体(AR)对前列腺癌细胞的生长至关重要。在这里，我们报告了AR的酪氨酸磷酸化是由生长因子诱导的，并且在激素不敏感的前列腺癌中升高。在雄激素耗竭的条件下，AR主要酪氨酸磷酸化位点的突变显著抑制前列腺癌细胞的生长。Src酪氨酸激酶似乎与AR的磷酸化有关，在人类前列腺癌中，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，生长因子及其下游酪氨酸激酶在激素消融治疗中升高，可以诱导AR的酪氨酸磷酸化，这种修饰可能在雄激素耗竭条件下对前列腺癌的生长起重要作用。
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.