Insulin-induced mitogenesis associated with transformation by the SV40 large T antigen.
Simian virus 40 (SV40) large T antigen-transformed cells typically show a markedly reduced serum requirement for growth and the inability to growth arrest and differentiate. An SV40 large T antigen-transformed 3T3 T cell line, CSV3-1, that can growth arrest and differentiate into adipocytes with high efficiency has, however, recently been described (Scott et al: Proc. Natl. Acad. Sci. U.S.A. 86:1652-1656, 1989; Estervig et al: J. Virol. 63:2718-2725, 1989; J. Cell. Physiol. 142:552-558, 1990). The results of the current studies using these cells show that whereas quiescent 3T3 T cells show no mitogenic response to insulin, quiescent CSV3-1 cells show a highly significant insulin-induced mitogenic responsiveness in the absence of other added growth factors. Maximum mitogenesis was observed at an insulin concentration of 1 microgram/ml, which induced 40-70% of the cells to undergo DNA synthesis within 48 hours. The half maximum response was achieved with 1-10 ng/ml of insulin. Insulin's mitogenic effect on CSV3-1 cells was evident under several different culture conditions that induce quiescence and was not mediated by any detectable autocrine growth factors that might make CSV3-1 cells competent to respond to insulin. In CSV3-1 cells insulin appears to act on its own receptor rather than on the IGF-1 receptor, because at comparable dosages IGF-1 is 10- to 100-fold less effective than insulin. Insulin also is shown to be a mitogen for another SV40-transformed cell line, CSV3-35, which can be growth arrested; in contrast insulin has no mitogenic effect on two control cell lines that are stably transfected with pSV2neo, a plasmid containing SV40 early promoter/enhancer but lacking large T antigen gene: These results suggest a significant relationship between SV40 T antigen-associated transformation and the expression of mitogenic responsiveness to insulin.
Wang
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HL
Department of Pathology, University of Tennessee Medical Center, Memphis 38163.
Scott
R E
RE
D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000502:physiology*; D015139:Blotting, Southern; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D003470:Culture Media; D015870:Gene Expression; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D008934:Mitogens; D011956:Receptors, Cell Surface / Q000502:physiology; D017451:Receptors, Somatomedin; D014162:Transfection
D000952:Antigens, Polyomavirus Transforming; D003470:Culture Media; D007328:Insulin; D008934:Mitogens; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin