IGF-1 receptor levels and the proliferation of young and senescent human fibroblasts.
We have investigated the role of the IGF-1 receptor in the proliferation of young and senescent human diploid fibroblasts. Using WI-38 cells, we have established the following: 1) both young and senescent cells have IGF-1 receptors, which can be autophosphorylated by IGF-1, the intensity of the autophosphorylation being roughly the same in both types of cells; 2) the levels of IGF-1 receptor mRNA are also similar in young and senescent cells; 3) both young and senescent cells have an absolute requirement for the IGF-1 receptor in order to be stimulated by either serum or SV40, respectively; 4) despite these similarities, young cells respond to IGF-1 (in combination with other growth factors) with DNA synthesis and mitosis, and senescent cells do not. We conclude that, although the IGF-1 receptor is still needed by senescent cells for a growth response to SV40, it is not, by itself, the determinant of senescence, at least in WI-38 cells.
Sell
C
C
Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107.
Ptasznik
A
A
Chang
C D
CD
Swantek
J
J
Cristofalo
V J
VJ
Baserga
R
R
D001483:Base Sequence; D002455:Cell Division; D002460:Cell Line; D016922:Cellular Senescence; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010766:Phosphorylation; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000378:metabolism*; D013539:Simian virus 40 / Q000235:genetics; D014158:Transcription, Genetic
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D012313:RNA; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1