TY - JOUR
T1 - Human telomerase catalytic subunit (hTERT) suppresses p53-mediated anti-apoptotic response via induction of basic fibroblast growth factor
AU - Jin, Xun
AU - Beck, Samuel
AU - Sohn, Young Woo
AU - Kim, Jun Kyum
AU - Kim, Sung Hak
AU - Yin, Jinlong
AU - Pian, Xumin
AU - Kim, Sung Chan
AU - Choi, Yun Jaie
AU - Kim, Hyunggee
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Cell death
KW - Fibroblast growth factor 2
KW - Telomerase
KW - Tumor suppressor protein p53
UR - http://www.scopus.com/inward/record.url?scp=77957361644&partnerID=8YFLogxK
U2 - 10.3858/emm.2010.42.8.058
DO - 10.3858/emm.2010.42.8.058
M3 - Article
C2 - 20628269
AN - SCOPUS:77957361644
SN - 1226-3613
VL - 42
SP - 574
EP - 582
JO - Experimental and Molecular Medicine
JF - Experimental and Molecular Medicine
IS - 8
ER -