Human telomerase catalytic subunit (hTERT) suppresses p53-mediated anti-apoptotic response via induction of basic fibroblast growth factor
Experimental & Molecular Medicine
;
: 574-582, 2010.
Artigo
em Inglês
| 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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Dano ao DNA
/
RNA Mensageiro
/
Linhagem Celular Transformada
/
Células HeLa
/
Regulação Neoplásica da Expressão Gênica
/
Fator 2 de Crescimento de Fibroblastos
/
Proteína Supressora de Tumor p53
/
Apoptose
/
Telomerase
/
Domínio Catalítico
Limite:
Humanos
Idioma:
Inglês
Revista:
Experimental & Molecular Medicine
Ano de publicação:
2010
Tipo de documento:
Artigo
Similares
MEDLINE
...
LILACS
LIS