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Adenovirus transformation revertant resistant to retransformation by E1 but not by SV40-T and HPV16-E7 oncogenes
S Sircar1, J Horvath, D Roberge
1Département de microbiologie, Faculté de médecine, Université de Sherbrooke, Québec, Canada.
Abstract:
We have previously described a revertant cell line which expresses a dominant tumor suppressor phenotype to E1 but not to heterologous oncogenes such as c-myc, N-ras, or polyoma middle t (Sircar et al. (1988) Oncogene 3, 725-728). DNA tumor virus oncogenes have been suggested to transform cells via the common mechanism of sequestering the Rb-105 antioncoprotein. This paradigm would predict that our revertant cell line, which is resistant to retransformation by E1a, should also be resistant to the other members of the Rb-105 binding family of oncogenes. To test this hypothesis we transfected the revertant cell line with plasmids bearing SV40-T or the HPV16-E7 oncogenes. Because transformation was obtained by both oncogenes at efficiencies similar to the transformation of a related revertant cell line, the results suggest that the resistance phenotype is specific to E1a. This specificity was further confirmed by cell fusion experiments.
Insights
A specific cell line resists tumor suppressor E1a but not other oncogenes like SV40-T or HPV16-E7. This suggests E1a
Area of Science:
- Oncogenesis
- Molecular Biology
- Cell Biology
Background:
- A previously developed revertant cell line exhibits a dominant tumor suppressor phenotype specifically against E1a, but not against other oncogenes.
- The prevailing hypothesis suggests that DNA tumor virus oncogenes transform cells by sequestering the retinoblastoma-associated protein (Rb-105).
Purpose of the Study:
- To investigate whether the observed resistance to E1a retransformation extends to other oncogenes that bind Rb-105.
- To determine if the resistance phenotype of the revertant cell line is specific to E1a.
Main Methods:
- Transfection of the revertant cell line with plasmids encoding SV40-T and HPV16-E7 oncogenes.
- Transformation efficiency assays comparing the revertant cell line to a related control cell line.
- Cell fusion experiments to further assess phenotype specificity.
Main Results:
- The revertant cell line was successfully transformed by both SV40-T and HPV16-E7 oncogenes at efficiencies comparable to a related control cell line.
- These findings indicate that the resistance to transformation is not a general resistance to Rb-105 binding oncogenes.
- Cell fusion experiments corroborated the specificity of the resistance phenotype for E1a.
Conclusions:
- The resistance to transformation observed in the revertant cell line is highly specific to the E1a oncogene.
- The mechanism of transformation by E1a may differ from that of other Rb-105 binding oncogenes, such as SV40-T and HPV16-E7.
- This specificity challenges the universal paradigm of Rb-105 sequestration as the sole mechanism for transformation by DNA tumor virus oncogenes.