Wang H L, Scott R E
Department of Pathology, University of Tennessee Medical Center, Memphis 38163.
J Cell Physiol. 1991 Apr;147(1):102-10. doi: 10.1002/jcp.1041470114.
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.
猴病毒40（SV40）大T抗原转化的细胞通常表现出对生长所需血清的显著减少以及无法生长停滞和分化。然而，最近已描述了一种SV40大T抗原转化的3T3 T细胞系CSV3-1，它能够高效地生长停滞并分化为脂肪细胞（斯科特等人：《美国国家科学院院刊》86:1652 - 1656，1989；埃斯特维格等人：《病毒学杂志》63:2718 - 2725，1989；《细胞生理学杂志》142:552 - 558，1990）。使用这些细胞的当前研究结果表明，静止的3T3 T细胞对胰岛素无促有丝分裂反应，而静止的CSV3-1细胞在没有添加其他生长因子的情况下显示出高度显著的胰岛素诱导的促有丝分裂反应性。在胰岛素浓度为1微克/毫升时观察到最大有丝分裂，这在48小时内诱导40 - 70%的细胞进行DNA合成。半最大反应在1 - 10纳克/毫升胰岛素时达到。胰岛素对CSV3-1细胞的促有丝分裂作用在几种诱导静止的不同培养条件下都很明显，并且不是由任何可检测到的自分泌生长因子介导的，这些自分泌生长因子可能使CSV3-1细胞有能力对胰岛素作出反应。在CSV3-1细胞中，胰岛素似乎作用于其自身受体而非胰岛素样生长因子-1（IGF-1）受体，因为在相当剂量下，IGF-1的效力比胰岛素低10至100倍。胰岛素也被证明是另一种可生长停滞且被SV40转化的细胞系CSV3-35的促有丝分裂原；相比之下，胰岛素对两个用pSV2neo稳定转染的对照细胞系无促有丝分裂作用，pSV2neo是一种含有SV40早期启动子/增强子但缺乏大T抗原基因的质粒：这些结果表明SV40 T抗原相关转化与对胰岛素的促有丝分裂反应性表达之间存在显著关系。
