Human telomerase catalytic subunit (hTERT) suppresses p53-mediated anti-apoptotic response via induction of basic fibroblast growth factor
Experimental & Molecular Medicine
;
: 574-582, 2010.
Article
in English
| WPRIM
| ID: wpr-200108
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
DNA Damage
/
RNA, Messenger
/
Cell Line, Transformed
/
HeLa Cells
/
Gene Expression Regulation, Neoplastic
/
Fibroblast Growth Factor 2
/
Tumor Suppressor Protein p53
/
Apoptosis
/
Telomerase
/
Catalytic Domain
Limits:
Humans
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2010
Type:
Article
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