Immortalization of human embryonic fibroblasts by overexpression of c-myc and simian virus 40 large T antigen.
- Author:
Hyun Seok KIM
1
;
Jong Yeon SHIN
;
Ji Yeon YUN
;
Duck Kyu AHN
;
Jae Yong LEE
Author Information
1. Department of Biochemistry, College of Medicine, Hallym University, Chunchon, Kangwon-do, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
immortalization;
human embryonic fibroblasts;
SV40 large T antigen;
telomerase
- MeSH:
Antigens, Polyomavirus Transforming/genetics/*metabolism;
Biological Markers;
Cell Aging/*genetics;
Cell Transformation, Viral;
Cells, Cultured;
Cyclins/metabolism;
Diploidy;
Fibroblasts/*metabolism;
Genes, myc/*genetics;
Human;
Protein p16/metabolism;
Simian virus 40/genetics;
Support, Non-U.S. Gov't;
Telomerase/metabolism
- From:Experimental & Molecular Medicine
2001;33(4):293-298
- CountryRepublic of Korea
- Language:English
-
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.
