Immortalization of human embryonic fibroblasts by overexpression of c-myc and simian virus 40 large T antigen
Experimental & Molecular Medicine
;
: 293-298, 2001.
Article
in English
| WPRIM
| ID: wpr-144616
ABSTRACT
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Biomarkers
/
Cell Transformation, Viral
/
Cells, Cultured
/
Antigens, Polyomavirus Transforming
/
Genes, myc
/
Cellular Senescence
/
Cyclins
/
Simian virus 40
/
Telomerase
/
Cyclin-Dependent Kinase Inhibitor p16
Limits:
Humans
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2001
Type:
Article
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