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Resistance to transformation by insertionally activated c-erbB is a dominant phenotype in fibroblasts
T H Carter1, N Dominguez, L Zeng
1William K. Warren Medical Research Institute, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
Abstract:
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.
Insights
Tissue-specific factors dictate cell transformation by erbB oncogenes. NIH/3T3 cells resist transformation by insertionally activated c-erbB (IAc-erbB), showing conserved fibroblast resistance across species.
Area of Science:
- Molecular Biology
- Oncology
- Cellular Biology
Background:
- Cell susceptibility to oncogene transformation varies by tissue type.
- Avian fibroblasts resist transformation by insertionally activated c-erbB (IAc-erbB), while erythroblasts are transformed.
- The epidermal growth factor receptor is implicated in these transformations.
Purpose of the Study:
- To investigate the susceptibility of NIH/3T3 cells to IAc-erbB transformation.
- To explore the interaction between IAc-erbB and v-erbB alleles in cellular transformation.
- To understand the tissue-specific regulatory mechanisms of receptor tyrosine kinases.
Main Methods:
- Transformation assays using NIH/3T3 cells with IAc-erbB.
- Co-expression studies of IAc-erbB and v-erbB alleles.
- Analysis of growth regulation effects in different cellular contexts.
Main Results:
- NIH/3T3 cells demonstrated resistance to transformation by IAc-erbB, conserving nonpermissiveness observed in avian fibroblasts.
- IAc-erbB expression inhibited transformation by a v-erbB allele, indicating trans-dominant interference.
- IAc-erbB exhibited context-dependent opposite growth effects (positive and negative regulation).
Conclusions:
- Fibroblast resistance to IAc-erbB is conserved across avian and murine species.
- IAc-erbB can mediate opposing growth signals based on cellular context, highlighting tissue-specific regulation.
- Understanding these tissue-specific inhibitory mechanisms is crucial for deciphering the tropism of erbB mutants.