Exp Mol Med.  2010 Aug;42(8):574-582. 10.3858/emm.2010.42.8.058.

Human telomerase catalytic subunit (hTERT) suppresses p53-mediated anti-apoptotic response via induction of basic fibroblast growth factor

• Jin X
• Beck S
• Sohn YW
• Kim JK
• Kim SH
• Yin J
• Pian X
• Kim SC
• Choi YJ
• Kim H

• KMID: 1104384
• DOI: http://doi.org/10.3858/emm.2010.42.8.058

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.

Keyword

apoptosis; cell death; fibroblast growth factor 2; telomerase; tumor suppressor protein p53

MeSH Terms

*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