Kolár Z, Murray P G, Madarova J, Lukesova M, Hlobilkova A, Riháková P, Flavell P, Strnad M, Student V, Vojtesek B
Laborator of Molecular Pathology; Faculty of Medicine, Palacky University and Faculty Hospital in Olomouc, Olomouc, 77515 Czech Republic.
Neoplasma. 2002;49(3):172-7.
The expression of several genes involved in apoptosis and cell cycle control can be regulated by steroid hormones and related agents via their nuclear receptors. Members of the bcl-2 gene family participate in the regulation of apoptosis in a diverse range of cell types and are implicated in the development of hormone refractory prostate cancer and resistance to anti-cancer therapy. The aim of this study, therefore, was to examine the expression of several nuclear receptors in relation to the expression of apoptosis and cell cycle related proteins in a series of patients with early hormone refractory prostate cancer. Analysis of protein expression revealed only a weak association between Bcl-2 and AR. Bax positivity and p27Kip1 expression were significantly more frequent in the AR-positive tumors, whereas RXRbeta expression was more frequently observed in the AR-negative group. The expression of AR, Bax and p27Kip1 was inversely related, and the expression of RXRbeta directly related, to Gleason pattern status. These results suggest that the immunophenotype of early hormone refractory prostate cancer may be different to that seen in more advanced stage disease. Androgen withdrawal therapy employing anti-androgens may elicit different signalling pathways that may be dependent on ARstatus and ARsensitivity.
凋亡和细胞周期调控相关的多个基因的表达可受类固醇激素及相关因子通过其核受体的调节。bcl-2基因家族成员参与多种细胞类型的凋亡调控，并与激素难治性前列腺癌的发生发展及抗癌治疗耐药相关。因此，本研究旨在检测一系列早期激素难治性前列腺癌患者中几种核受体的表达，并分析其与凋亡及细胞周期相关蛋白表达的关系。蛋白质表达分析显示，Bcl-2与AR之间仅有微弱关联。在AR阳性肿瘤中，Bax阳性和p27Kip1表达显著更常见，而在AR阴性组中，RXRβ表达更常见。AR、Bax和p27Kip1的表达呈负相关，而RXRβ的表达与Gleason分级状态呈正相关。这些结果提示，早期激素难治性前列腺癌的免疫表型可能与更晚期疾病不同。使用抗雄激素的雄激素剥夺疗法可能引发不同的信号通路，这可能取决于AR状态和AR敏感性。
