PMID: 8993830Jan 1, 1997Paper

Ras(leu61) blocks differentiation of transformable 3T3 L1 and C3H10T1/2-derived preadipocytes in a dose- and time-dependent manner

Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research
L RaptisT Haliotis

Abstract

To investigate the functional relationship between the transforming ability of Ras and its role as an integral component of the differentiation-promoting insulin signaling pathway, we introduced a leu61-activated ras gene into the Ras-transformable 3T3 L1 (ATCC CCL92.1) and a number of C3H10T1/2-derived preadipocytic cell lines. The results demonstrate a quantitative reciprocal regulation of differentiation and several transformation-associated properties in response to graded levels of ras gene expression, with the loss of differentiative capacity, morphological transformation, stimulation of proliferation, and anchorage-independent growth requiring increasing levels of Ras(leu61) protein. Furthermore, using novel, tightly regulatable 3T3 L1 transfectants, we demonstrated that Ras(leu61) effectiveness in blocking adipocytic differentiation is strictly dependent on the timing of its expression relative to cell growth arrest, with ras(leu61) expression being ineffective at inhibiting differentiation or inducing morphological transformation once the differentiative process has commenced. Moreover, rasleu61 induction failed to substitute for or enhance the c-Ras-dependent differentiative insulin signal, even under conditions in wh...Continue Reading

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