p16INK4a downregulation is involved in immortalization of primary human prostate epithelial cells induced by telomerase
p16INK4a downregulation is involved in immortalization of primary human prostate epithelial cells induced by telomerase
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DOI：
10.1002/mc.20434
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发表时间：
2008-10-01
影响因子：
4.6
通讯作者：
Zhao, Yongliang
中科院分区：
文献类型：
--
作者：
Shao, Genze;Balajee, Adayabalam S.;Zhao, Yongliang
前列腺癌是男性癌症死亡的主要原因。因此，开发合适的模型系统对于理解前列腺癌进展的分子基础至关重要。在这项研究中，将人类端粒酶（hTERT）引入正常的人前列腺上皮细胞（PrECs），使其端粒酶活性提高，端粒长度延长，增殖寿命延长。利用hTERT转染技术，建立了端粒长度稳定的PrEC-hTERT细胞系的不朽大规模培养。然而，单独激活hTERT似乎不足以实现PrEC细胞的永生化，因为p16（INK4a）启动子的甲基化已被发现参与永生化过程。p53功能完整，在永生化的PrECs中未发现p53基因突变。此外，不朽的PrECs显示出接近二倍体的染色体补体，尽管鉴定出一些互惠和非互惠易位。它们是锚定依赖性的，在免疫抑制的宿主动物中不形成肿瘤。因此，恶性前转化的人类PrECs为前列腺癌的研究提供了一个有价值的模型。(C) 2008 Wiley-Liss, Inc。
Prostate cancer is a major cause of cancer death among male population. Therefore, development of appropriate model systems is critical for understanding the molecular basis of prostate cancer progression. In this study, introduction of human telomerase (hTERT) into normal human prostate epithelial cells (PrECs) renders them higher telomerase activity, elongated telomere length and an extended proliferative lifespan. The immortal mass culture of PrEC-hTERT cell line with stabilized telomere length has been established using hTERT transfection. However, activation of hTERT alone appears to be insufficient for immortalization of PrEC cells because methylation of p16(INK4a) promoter has been found to be involved in the immortalization process. p53 was functionally intact and no mutations of p53 gene were identified in the immortalized PrECs. In addition, the immortal PrECs show a near diploid complement of chromosomes albeit a few reciprocal and non-reciprocal translocations are identified. They are anchorage dependent and do not form tumors in immunosuppressed host animals. Therefore, premalignantly transformed human PrECs provide a valuable model for prostate cancer research. (C) 2008 Wiley-Liss, Inc.