TY - JOUR
T1 - Failure of senescent human fibroblasts to express the insulin-like growth factor-1 gene
AU - Ferber, Andres
AU - Chang, Chung Der
AU - Sell, Christian
AU - Ptasznik, Andrej
AU - Cristofalo, Vincent J.
AU - Hubbard, Karen
AU - Ozer, Harvey L.
AU - Adamo, Martin
AU - Roberts, Charles T.
AU - LeRoith, Derek
AU - Dumenil, Guillaume
AU - Baserga, Renato
PY - 1993/8/25
Y1 - 1993/8/25
N2 - Senescent human diploid fibroblasts express several growth-regulated genes but fail to express others. In this paper we show, by a very sensitive technique (reverse transcriptase-polymerase chain reaction), that senescent cells fail to express insulin-like growth factor-1 (IGF-1) mRNA, which is expressed in moderate amounts by young cells. Human fibroblasts immortalized by transfection with a temperature-sensitive SV40 T antigen gene regain the ability to express IGF-1 mRNA, but only at the permissive temperature of 34°C. Under these conditions, the immortalized human fibroblasts grow even in 1% serum. At the restrictive temperature of 39°C, the temperature-sensitive T antigen is nonfunctional, IGF-1 RNA is not detectable, and the cells fail to grow even in 10% serum. The failure to express IGF-1 mRNA in postsenescent cells can be ascribed, at least in part, to a transcriptional mechanism. Despite the correlation among immortalization by SV40 T antigen, expression of IGF-1, and growth, it seems unlikely that the failure to express IGF-1 is the sole cause of cellular senescence; other requirements must be postulated.
AB - Senescent human diploid fibroblasts express several growth-regulated genes but fail to express others. In this paper we show, by a very sensitive technique (reverse transcriptase-polymerase chain reaction), that senescent cells fail to express insulin-like growth factor-1 (IGF-1) mRNA, which is expressed in moderate amounts by young cells. Human fibroblasts immortalized by transfection with a temperature-sensitive SV40 T antigen gene regain the ability to express IGF-1 mRNA, but only at the permissive temperature of 34°C. Under these conditions, the immortalized human fibroblasts grow even in 1% serum. At the restrictive temperature of 39°C, the temperature-sensitive T antigen is nonfunctional, IGF-1 RNA is not detectable, and the cells fail to grow even in 10% serum. The failure to express IGF-1 mRNA in postsenescent cells can be ascribed, at least in part, to a transcriptional mechanism. Despite the correlation among immortalization by SV40 T antigen, expression of IGF-1, and growth, it seems unlikely that the failure to express IGF-1 is the sole cause of cellular senescence; other requirements must be postulated.
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M3 - Article
C2 - 7688732
AN - SCOPUS:0027295499
SN - 0021-9258
VL - 268
SP - 17883
EP - 17888
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 24
ER -