Beham A W, Sarkiss M, Brisbay S, Tu S M, von Eschenbach A C, McDonnell T J
Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Int J Mol Med. 1998 Jun;1(6):953-9. doi: 10.3892/ijmm.1.6.953.
Androgen-independent growth of prostate cancer is correlated with expression of bcl-2. The impact of bcl-2 expression on the growth of prostate cancer cells following androgen ablation, was examined in the androgen-sensitive prostatic carcinoma cell line, LNCaP. Vector control and bcl-2 expressing LNCaP cells were grown subcutaneously in male nude mice. Tumor volume, apoptosis, and proliferation were assessed following castration. The levels of c-myc, p53, p21, bax, and bcl-2 protein were assessed by Western blotting. Bcl-2 expressing tumors exhibited a significant augmentation in growth compared to controls (p 0.01). No difference in the spontaneous rate of proliferation was observed between bcl-2 and control tumors, however, bcl-2 expressing tumors exhibited lower rates of apoptosis. Following orchiectomy the apoptotic index remained significantly lower in bcl-2 expressing tumors (p 0.002 at day 3). The proliferative index was maintained in bcl-2 expressing, but not control tumors following castration. This resulted in a significant growth advantage in bcl-2 tumors subsequent to androgen ablation (p 0.001). These changes were accompanied by alterations in the levels of gene products known to regulate the cell cycle and/or apoptosis. These results emphasize the significance of bcl-2 expression during prostate cancer progression and suggest possible mechanisms for the acquisition of androgen-independent tumor growth.
前列腺癌的雄激素非依赖性生长与bcl-2的表达相关。在雄激素敏感的前列腺癌细胞系LNCaP中，研究了bcl-2表达对雄激素去除后前列腺癌细胞生长的影响。将载体对照和表达bcl-2的LNCaP细胞接种于雄性裸鼠皮下。去势后评估肿瘤体积、凋亡和增殖情况。通过蛋白质印迹法评估c-myc、p53、p21、bax和bcl-2蛋白的水平。与对照相比，表达bcl-2的肿瘤生长显著增加（p<0.01）。在bcl-2和对照肿瘤之间未观察到自发增殖率的差异，然而，表达bcl-2的肿瘤凋亡率较低。去势后，表达bcl-2的肿瘤凋亡指数在第3天仍显著较低（p<0.002）。去势后，表达bcl-2的肿瘤维持增殖指数，但对照肿瘤则不然。这导致雄激素去除后bcl-2肿瘤具有显著的生长优势（p<0.001）。这些变化伴随着已知调节细胞周期和/或凋亡的基因产物水平的改变。这些结果强调了bcl-2表达在前列腺癌进展过程中的重要性，并提示了获得雄激素非依赖性肿瘤生长的可能机制。
