Resistance to transformation by insertionally activated c-erbB is a dominant phenotype in fibroblasts.
Tissue-specific factors influence whether cells are susceptible to transformation by erbB oncogenes. Avian fibroblasts resist transformation by insertionally activated c-erbB (IAc-erbB), whereas erythroblasts are transformed by this mutant of the epidermal growth factor receptor. In studies presented here, NIH/3T3 cells resisted transformation by IAc-erbB. This finding indicates that the nonpermissiveness of fibroblasts is conserved between avian and murine species. Surprisingly, expression of IAc-erbB blocked transformation by a v-erbB allele. The trans-dominant interference by IAc-erbB occurred despite expression at levels lower than for v-erbB. Together with previous reports, the results indicate that IAc-erbB can exert opposite growth effects in different tissues. The switch from positive to negative growth regulation, which depends on the cellular context, provides novel insight into tissue-specific regulation of receptor tyrosine kinases. Evasion of cell-specific inhibition apparently contributes to the distinct tissue tropisms of various erbB mutants.
Carter
T H
TH
William K. Warren Medical Research Institute, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
Dominguez
N
N
Zeng
L
L
Kung
H J
HJ
D016475:3T3 Cells; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D005347:Fibroblasts; D005799:Genes, Dominant; D018734:Genes, erbB-2; D051379:Mice; D008969:Molecular Sequence Data; D009857:Oncogenes; D010641:Phenotype
D017931:DNA Primers