RhoB Is Dispensable for Mouse Development, but It Modifies Susceptibility to Tumor Formation as Well as Cell Adhesion and Growth Factor Signaling in Transformed Cells

Author:

Liu Ai-Xue1,Rane Neena1,Liu Jeh-Ping2,Prendergast George C.13

Affiliation:

1. The Wistar Institute, Philadelphia, 1 and

2. Center for Neurobiology and Behavior, Columbia University, New York, New York2

3. The DuPont Pharmaceuticals Company, Glenolden Laboratory, Glenolden, 3 Pennsylvania, and

Abstract

ABSTRACT RhoB is an endosomal small GTPase that is implicated in the response to growth factors, genotoxic stress, and farnesyltransferase inhibitors. To gain insight into its physiological functions we examined the consequences of homozygous gene deletion in the mouse. Loss of RhoB did not adversely affect mouse development, fertility, or wound healing. However, embryo fibroblasts cultured in vitro exhibited a defect in motility, suggesting that RhoB has a role in this process that is conditional on cell stress. Neoplastic transformation by adenovirus E1A and mutant Ras yielded differences in cell attachment and spreading that were not apparent in primary cells. In addition, transformed −/− cells displayed altered actin and proliferative responses to transforming growth factor β. A negative modifier role in transformation was suggested by the increased susceptibility of −/− mice to 7,12-dimethylbenz[ a ]anthracene-induced skin carcinogenesis and by the increased efficiency of intraperitoneal tumor formation by −/− cells. Our findings suggest that RhoB is a negative regulator of integrin and growth factor signals that are involved in neoplastic transformation and possibly other stress or disease states.

Publisher

American Society for Microbiology

Subject

Cell Biology,Molecular Biology

Reference27 articles.

1. Intracellular localization of the p21rho proteins;Adamson P.;J. Cell Biol.,1992

2. Mutagenesis of the Ha-ras oncogene in mouse skin tumors induced by polycyclic aromatic hydrocarbons;Bizub D.;Proc. Natl. Acad. Sci. USA,1986

3. Cell Growth Inhibition by Farnesyltransferase Inhibitors Is Mediated by Gain of Geranylgeranylated RhoB

4. Geranylgeranylated RhoB mediates inhibition of human tumor cell growth by farnesyltransferase inhibitors;Du W.;Cancer Res.,1999

5. RhoB is stabilized by transforming growth factor β and antagonizes transcriptional activation;Engel M. E.;J. Biol. Chem.,1998

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