Differential effects of c-Ras upon transformation, adipocytic differentiation, and apoptosis mediated by the simian virus 40 large tumor antigen

Anagnostopoulou, A., Jun Cao, Rozanne Arulanandam, Adina Vultur and Leda Raptis 2007. Differential effects of c-Ras upon transformation, adipocytic differentiation, and apoptosis mediated by the simian virus 40 large tumor antigen. Biochemistry and Cell Biology. 85 (1), pp. 32-48. https://doi.org/10.1139/o06-187

TitleDifferential effects of c-Ras upon transformation, adipocytic differentiation, and apoptosis mediated by the simian virus 40 large tumor antigen
TypeJournal article
AuthorsAnagnostopoulou, A., Jun Cao, Rozanne Arulanandam, Adina Vultur and Leda Raptis
Abstract

To investigate the functional relationship between the ability of the simian virus 40 large tumor antigen (TAg) to transform and its ability to block adipocytic differentiation and induce apoptosis, we expressed TAg in C3H10T1/2 (10T1/2)-derived preadipocytes. The results demonstrated that differentiation could be suppressed at lower TAg levels than at the levels required for full neoplastic conversion. Progressively higher TAg levels were accompanied by apoptosis induction in this system. To further examine the role of the cellular Ras protooncogene product (Ras) in TAg function, TAg was expressed in 10T1/2-derived preadipocytes rendered deficient in Ras activity by transfection with inducible or constitutive antisense ras gene constructs. The results indicated that Ras is required for TAg-mediated transformation and for suppression of adipocytic differentiation, while TAg-mediated apoptosis following serum starvation was independent from Ras action. Unexpectedly, our results further demonstrated a dramatic reduction in the levels of the TAg protein itself as differentiation progressed in Ras-knockdown cells, with a concomitant reduction in TAg’s ability to induce apoptosis as a result. These findings suggest that Ras, although cytoplasmic, is an integral component of the pathway whereby TAg, an oncoprotein believed to have primarily nuclear targets, suppresses differentiation or induces neoplastic conversion of murine preadipocytes.

JournalBiochemistry and Cell Biology
Journal citation85 (1), pp. 32-48
ISSN0829-8211
1208-6002
Year2007
PublisherNRC Research Press
Digital Object Identifier (DOI)https://doi.org/10.1139/o06-187
Web address (URL)http://dx.doi.org/10.1139/o06-187
Publication dates
PublishedFeb 2007

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