Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Int J Mol Sci. 2013 Aug 13;14(8):16656-71. doi: 10.3390/ijms140816656.
We previously reported that AR phosphorylation at serine 213 was associated with poor outcome and may contribute to prostate cancer development and progression. This study investigates if specific AR phosphorylation sites have differing roles in the progression of hormone naïve prostate cancer (HNPC) to castrate resistant disease (CRPC). A panel of phosphospecific antibodies were employed to study AR phosphorylation in 84 matched HNPC and CRPC tumours. Immunohistochemistry measured Androgen receptor expression phosphorylated at serine residues 94 (pAR94), 308 (pAR308), 650(pAR650) and 791 (pAR791). No correlations with clinical parameters were observed for pAR94 or pAR650 in HNPC or CRPC tumours. In contrast to our previous observation with serine 213, high pAR308 is significantly associated with a longer time to disease specific death (p = 0.011) and high pAR791 expression significantly associated with a longer time to disease recurrence (p = 0.018) in HNPC tumours and longer time to death from disease recurrence (p = 0.040) in CRPC tumours. This observation in CRPC tumours was attenuated in high apoptotic tumours (p = 0.022) and low proliferating tumours (p = 0.004). These results demonstrate that understanding the differing roles of AR phosphorylation is necessary before this can be exploited as a target for castrate resistant prostate cancer.
我们之前曾报道过，丝氨酸 213 上的 AR 磷酸化与不良预后相关，可能有助于前列腺癌的发展和进展。本研究调查了特定的 AR 磷酸化位点是否在激素初治前列腺癌（HNPC）向去势抵抗性疾病（CRPC）的进展中具有不同的作用。我们使用一组磷酸特异性抗体研究了 84 对匹配的 HNPC 和 CRPC 肿瘤中的 AR 磷酸化。免疫组织化学测量了丝氨酸残基 94（pAR94）、308（pAR308）、650（pAR650）和 791（pAR791）处雄激素受体表达的磷酸化。在 HNPC 或 CRPC 肿瘤中，pAR94 或 pAR650 与临床参数均无相关性。与我们之前关于丝氨酸 213 的观察结果相反，在 HNPC 肿瘤中，高 pAR308 与疾病特异性死亡时间延长显著相关（p = 0.011），高 pAR791 表达与疾病复发时间延长显著相关（p = 0.018），在 CRPC 肿瘤中，与疾病复发导致的死亡时间延长显著相关（p = 0.040）。在高凋亡肿瘤（p = 0.022）和低增殖肿瘤（p = 0.004）中，这种在 CRPC 肿瘤中的观察结果减弱。这些结果表明，在将 AR 磷酸化作为去势抵抗性前列腺癌的靶点加以利用之前，有必要了解 AR 磷酸化的不同作用。
