Phosphorylation of the androgen receptor is associated with reduced survival in hormone-refractory prostate cancer patients.
Phosphorylation of the androgen receptor is associated with reduced survival in hormone-refractory prostate cancer patients.
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雄激素受体的磷酸化与激素难治性前列腺癌患者的生存率降低有关。
DOI：
10.1038/sj.bjc.6604152
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发表时间：
2008-03-25
影响因子：
8.8
通讯作者：
Edwards, J.
中科院分区：
文献类型：
--
作者：
McCall, P.;Gemmell, L. K.;Mukherjee, R.;Bartlett, J. M. S.;Edwards, J.
细胞系研究表明，PI 3 K/Akt通路在难治性前列腺癌（HRPC）中上调，并可导致雄激素受体（AR）磷酸化。因此，本研究旨在确定这是否与临床HRPC的发展相关。采用免疫组化研究Akt和AR在来自68名患者的相匹配的前列腺癌敏感性和难治性肿瘤中的表达和磷酸化状态。在难治性组织中，只有磷酸化AR（pAR）与复发至死亡时间较短相关（P=0.003）。然而，当研究从前列腺癌敏感性向难治性转变中表达的增加时，PI 3 K表达的增加与生化复发时间的减少相关（P=0.014），pAkt 473和pAR 210表达的增加与疾病特异性生存期的减少相关（分别为P=0.0019和0.0015）。pAkt 473和pAR 210的蛋白质表达也强相关（P<0.001，c.c.= 0.0001）。0.711）在激素难治性前列腺肿瘤中。这些结果使用临床样本提供了证据，证明PI 3 K/Akt途径的上调与HRPC发育期间AR的磷酸化相关，表明该途径可能是潜在的治疗靶点。
Cell line studies demonstrate that the PI3K/Akt pathway is upregulated in hormone-refractory prostate cancer (HRPC) and can result in phosphorylation of the androgen receptor (AR). The current study therefore aims to establish if this has relevance to the development of clinical HRPC. Immunohistochemistry was employed to investigate the expression and phosphorylation status of Akt and AR in matched hormone-sensitive and -refractory prostate cancer tumours from 68 patients. In the hormone-refractory tissue, only phosphorylated AR (pAR) was associated with shorter time to death from relapse (P=0.003). However, when an increase in expression in the transition from hormone-sensitive to -refractory prostate cancer was investigated, an increase in expression of PI3K was associated with decreased time to biochemical relapse (P=0.014), and an increase in expression of pAkt473 and pAR210 were associated with decreased disease-specific survival (P=0.0019 and 0.0015, respectively). Protein expression of pAkt473 and pAR210 also strongly correlated (P<0.001, c.c.=0.711) in the hormone-refractory prostate tumours. These results provide evidence using clinical specimens, that upregulation of the PI3K/Akt pathway is associated with phosphorylation of the AR during development of HRPC, suggesting that this pathway could be a potential therapeutic target.
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