Examination of human tumors for rhoA mutations.
rhoA encodes a ras-related GTP-binding protein that is thought to play a role in cytoskeletal organization. Recent evidence has suggested both that rhoA could act either as a dominant oncogene, since transfection of both normal and activated rho genes confer a transformed phenotype on fibroblast cells in culture, or as a recessive tumor suppressor gene, by virtue, in part, of its chromosomal location at 3p21, a site deleted in many human malignancies. In either case, a role for rhoA in the oncogenesis of human tumors would be supported by the finding of rhoA mutations in tumors. We therefore examined human tumors and cell lines for mutations in the protein coding regions of rhoA by RNAase protection analysis. We first examined the expression of rhoA in renal cell carcinoma cell lines in which 3p21 was heterozygously deleted or retained. We found no evidence for rhoA mutations in these specimens. We also examined RNA from lung, breast, colon or ovarian tumors and also found no evidence of activating rhoA mutations. Furthermore, there was no relation between the level of rhoA mRNA expression and the presence or absence of 3p21 deletions in the renal cell carcinoma specimens. Thus, although rhoA has transforming potential in vitro, there is no evidence that it is activated by mutation in human malignancies, or that it could act as a tumor suppressor gene in tumors in which 3p21 is deleted.
Moscow
J A
JA
Medicine Branch, National Cancer Institute, Bethesda, MD 20892.
He
R
R
Gnarra
J R
JR
Knutsen
T
T
Weng
Y
Y
Zhao
W P
WP
Whang-Peng
J
J
Linehan
W M
WM
Cowan
K H
KH
D002292:Carcinoma, Renal Cell / Q000235:genetics; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D019204:GTP-Binding Proteins / Q000032:analysis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured; D020742:rhoA GTP-Binding Protein
D012333:RNA, Messenger; D019204:GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein