Failure of senescent human fibroblasts to express the insulin-like growth factor-1 gene.
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 degrees C. Under these conditions, the immortalized human fibroblasts grow even in 1% serum. At the restrictive temperature of 39 degrees 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.
Ferber
A
A
Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Chang
C
C
Sell
C
C
Ptasznik
A
A
Cristofalo
V J
VJ
Hubbard
K
K
Ozer
H L
HL
Adamo
M
M
Roberts
C T
CT
LeRoith
D
D
D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D001483:Base Sequence; D002460:Cell Line; D016922:Cellular Senescence / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics*; D008156:Luciferases / Q000096:biosynthesis / Q000378:metabolism; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism*; D012194:RNA-Directed DNA Polymerase; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D013539:Simian virus 40 / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D000952:Antigens, Polyomavirus Transforming; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D008156:Luciferases; D017526:Receptor, IGF Type 1; D012194:RNA-Directed DNA Polymerase