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KMID : 0620920010330040293
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Experimental & Molecular Medicine
2001 Volume.33 No. 4 p.293 ~ p.298
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Immortalization of human embryonic fibroblasts by overexpression of c-myc and simian virus 40 large T antigen
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Jae Yong Lee/Hyun Seok Kim
Jong Yeon Shin/Ji Yeon Yun/Duck Kyu Ahn/Jae Yong Lee
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Abstract
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SV40 large T antigen, a viral oncoprotein, is known to immortalize human diploid fibroblast by soaking up cellular RB and p53, but its frequency is extremely low. Additional genetic alteration is necessary for single-step immortalization. We attempted to find out what this alteration is by overexpressing cellular signal mediator genes; c-myc and cyclin D frequently amplified in many cancer cells. Overexpression of cyclin D did not affect the immortalization, but, overexpression of c-myc along with T antigen could immortalize normal human diploid fibroblast. Several cellular markers tested during immortalization process showed that p21, a cyclin-dependent kinase inhibitor and a marker of cellular senescence, disappeared in the life span-extended cells by T antigen and in the immortalized cells by c-myc. p21 was, however, elevated in the senescent cells and in the cells of crisis. Interestingly, p16 was upregulated whenever T antigen is overexpressed. Telomerase activity was also activated only in the immortalized cells. These results suggest that overexpression of c-myc contributes to immortalization of human diploid fibroblast by activating telomerase activity and suppressing p21 activity.
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KEYWORD
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immortalization, human embryonic fibroblasts, SV40 large T antigen, telomerase,
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