Human telomerase catalytic subunit (hTERT) suppresses p53-mediated anti-apoptotic response via induction of basic fibroblast growth factor.
10.3858/emm.2010.42.8.058
- Author:
Xun JIN
1
;
Samuel BECK
;
Young Woo SOHN
;
Jun Kyum KIM
;
Sung Hak KIM
;
Jinlong YIN
;
Xumin PIAN
;
Sung Chan KIM
;
Yun Jaie CHOI
;
Hyunggee KIM
Author Information
1. Cell Growth Regulation Laboratory (CGRL), School of Life Sciences and Biotechnology, Korea University, Seoul 136-713, Korea. hg-kim@korea.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
apoptosis;
cell death;
fibroblast growth factor 2;
telomerase;
tumor suppressor protein p53
- MeSH:
*Apoptosis;
*Catalytic Domain;
Cell Line, Transformed;
Cell Proliferation;
DNA Damage;
Fetus/cytology;
Fibroblast Growth Factor 2/*genetics/metabolism;
Fibroblasts/cytology/metabolism;
Gene Expression Regulation, Neoplastic;
Hela Cells;
Humans;
RNA, Messenger/genetics/metabolism;
Telomerase/deficiency/*metabolism;
Tumor Suppressor Protein p53/*metabolism
- From:Experimental & Molecular Medicine
2010;42(8):574-582
- CountryRepublic of Korea
- Language:English
-
Abstract:
Although human telomerase catalytic subunit (TERT) has several cellular functions including telomere homeostasis, genomic stability, cell proliferation, and tumorigenesis, the molecular mechanism underlying anti-apoptosis regulated by TERT remains to be elucidated. Here, we show that ectopic expression of TERT in spontaneously immortalized human fetal fibroblast (HFFS) cells, which are a telomerase- and p53-positive, leads to increases of cell proliferation and transformation, as well as a resistance to DNA damage response and inactivation of p53 function. We found that TERT and a mutant TERT (no telomerase activity) induce expression of basic fibroblast growth factor (bFGF), and ectopic expression of bFGF also allows cells to be resistant to DNA-damaging response and to suppress activation of p53 function under DNA-damaging induction. Furthermore, loss of TERT or bFGF markedly increases a p53 activity and DNA-damage sensitivity in HFFS, HeLa and U87MG cells. Therefore, our findings indicate that a novel TERT-bFGF axis accelerates the inactivation of p53 and consequent increase of resistance to DNA-damage response.
