Department of Urology, The First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
Cancer Res. 2011 Mar 15;71(6):2193-202. doi: 10.1158/0008-5472.CAN-10-1791. Epub 2011 Mar 8.
PrLZ/PC-1 is a newly identified, prostate-specific and androgen-inducible gene. Our previous study showed that PrLZ can enhance the proliferation and invasive capability of LNCaP cells, contributing to the development of prostate cancer. However, its potential role in androgen-independent processes remains elusive. In this study, we showed that PrLZ enhanced in vitro growth and colony formation of prostate cancer cells on androgen deprivation as well as tumorigenicity in castrated nude mice. In addition, PrLZ stabilized mitochondrial transmembrane potential, prevented release of cytochrome c from mitochondria to cytoplasm, and inhibited intrinsic apoptosis induced by androgen depletion. Mechanistically, PrLZ elevated the phosphorylation of Akt and Stat3 and upregulated Bcl-2 expression. Our data indicate that PrLZ protects prostate cancer cells from apoptosis and promotes tumor progression following androgen deprivation. In summary, we propose that PrLZ is a novel antiapoptotic gene that is specifically activated in prostate cancer cells escaping androgen deprivation may offer an appealing therapeutic target to prevent or treat advanced prostate malignancy.
PLZ/PC-1 是一个新鉴定的、前列腺特异性和雄激素诱导的基因。我们之前的研究表明，PLZ 可以增强 LNCaP 细胞的增殖和侵袭能力，促进前列腺癌的发展。然而，它在雄激素非依赖性过程中的潜在作用仍然难以捉摸。在这项研究中，我们表明 PLZ 增强了前列腺癌细胞在去雄激素剥夺时的体外生长和集落形成能力，以及在去势裸鼠中的致瘤性。此外，PLZ 稳定了线粒体跨膜电位，防止细胞色素 c 从线粒体释放到细胞质，并抑制雄激素耗竭诱导的内在凋亡。在机制上，PLZ 提高了 Akt 和 Stat3 的磷酸化水平，并上调了 Bcl-2 的表达。我们的数据表明，PLZ 可以保护前列腺癌细胞免受凋亡，并促进去雄激素后肿瘤的进展。综上所述，我们提出 PLZ 是一种新型的抗凋亡基因，它在逃避雄激素剥夺的前列腺癌细胞中特异性激活，可能为预防或治疗晚期前列腺恶性肿瘤提供一个有吸引力的治疗靶点。
