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KMID : 0620920100420080574
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Experimental & Molecular Medicine
2010 Volume.42 No. 8 p.574 ~ p.582
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Human telomerase catalytic subunit (hTERT) suppresses p53-mediated anti-apoptotic response via induction of basic fibroblast growth factor
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Jin Xun
Choi Yun-Jaie
Kim Sung-Chan
Sohn Young-Woo
Kim Jun-Kyum
Kim Sung-Hak
Pian Xumin
Kim Hyung-Gee
Beck Samuel
Yin Jinlong
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Abstract
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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.
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KEYWORD
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apoptosis, cell death, fibroblast growth factor 2, telomerase, tumor suppressor protein p53
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