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.
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 beta. 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.
Liu
A X
AX
The Wistar Institute, Philadelphia, Pennsylvania, USA.
Rane
N
N
Liu
J P
JP
Prendergast
G C
GC
D015127:9,10-Dimethyl-1,2-benzanthracene; D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002273:Carcinogens; D002448:Cell Adhesion; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D006133:Growth Substances / Q000378:metabolism*; D006720:Homozygote; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000139:chemically induced; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D020743:rhoB GTP-Binding Protein / Q000235:genetics* / Q000502:physiology*
D000199:Actins; D002273:Carcinogens; D005353:Fibronectins; D006133:Growth Substances; D016212:Transforming Growth Factor beta; D015127:9,10-Dimethyl-1,2-benzanthracene; D020743:rhoB GTP-Binding Protein