A. Ferber et al., FAILURE OF SENESCENT HUMAN FIBROBLASTS TO EXPRESS THE INSULIN-LIKE GROWTH FACTOR-I GENE, The Journal of biological chemistry, 268(24), 1993, pp. 17883-17888
Senescent human diploid fibroblasts express several growth-regulated g
enes but fail to express others. In this paper we show, by a very sens
itive technique (reverse transcriptase-polymerase chain reaction), tha
t senescent cells fail to express insulin-like growth factor-1 (IGF-1)
mRNA, which is expressed in moderate amounts by young cells. Human fi
broblasts immortalized by transfection with a temperature-sensitive SV
40 T antigen gene regain the ability to express IGF-1 mRNA, but only a
t the permissive temperature of 34-degrees-C. Under these conditions,
the immortalized human fibroblasts grow even in 1% serum. At the restr
ictive temperature of 39-degrees-C, the temperature-sensitive T antige
n 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 postsene
scent cells can be ascribed, at least in part, to a transcriptional me
chanism. Despite the correlation among immortalization by SV40 T antig
en, expression of IGF-1, and growth, it seems unlikely that the failur
e to express IGF-1 is the sole cause of cellular senescence; other req
uirements must be postulated.