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p16 INK4a downregulation is involved in immortalization of primary human prostate epithelial cells induced by telomerase
Author(s) -
Shao Genze,
Balajee Adayabalam S.,
Hei Tom K.,
Zhao Yongliang
Publication year - 2008
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20434
Subject(s) - telomerase , telomere , telomerase reverse transcriptase , biology , prostate cancer , cancer research , prostate , cancer , transfection , population , stromal cell , cell culture , gene , genetics , medicine , environmental health
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. © 2008 Wiley‐Liss, Inc.