Selective induction of c-jun and jun-B but not c-fos or c-myc during mitogenesis in SV40-transformed cells at the predifferentiation growth arrest state.
Insulin has recently been reported to function as a complete mitogen for SV40 large T antigen-transformed 3T3 T-cells, designated CSV3-1, but not for nontransformed 3T3 T-cells (H. Wang and R. E. Scott, J. Cell. Physiol., 147: 102-110, 1991). It is now reported that sodium orthovanadate mimics this effect of insulin. For example, when exposed to 1-5 microM vanadate, most predifferentiation growth-arrested CSV3-1 cells undergo DNA synthesis within 24 h, but neither vanadate nor insulin induces mitogenesis in nontransformed 3T3 T-cells. To investigate the possible mechanisms by which mitogenesis is induced in CSV3-1 cells, the effects of insulin and vanadate on the expression of growth-related genes were examined. Whereas insulin and vanadate had no effect on the expression of c-fos, c-myc, c-jun, jun-B, or ornithine decarboxylase activity in nontransformed 3T3 T-cells, insulin and vanadate showed different effects on the expression of these genes in CSV3-1 cells. Insulin induced a rapid and transient accumulation of c-fos mRNA followed by induction of c-myc, c-jun, jun-B, and ornithine decarboxylase. In contrast, vanadate induced the expression of c-jun, jun-B, and ornithine decarboxylase without inducing c-fos and c-myc. These observations suggest that SV40 large T antigen may play an important role in insulin- and vanadate-induced mitogenesis and that insulin and vanadate may mediate their mitogenic effects by different signal transduction pathways.
Wang
H
H
Department of Pathology, University of Tennessee Medical Center, Memphis.
Wang
J Y
JY
Johnson
L R
LR
Scott
R E
RE
D000957:Antigens, Viral, Tumor / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D016762:Genes, fos / Q000235:genetics*; D016758:Genes, jun / Q000235:genetics*; D016259:Genes, myc / Q000235:genetics*; D007328:Insulin / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013539:Simian virus 40 / Q000235:genetics*; D013997:Time Factors; D014638:Vanadates / Q000494:pharmacology
D000957:Antigens, Viral, Tumor; D007328:Insulin; D014638:Vanadates