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Suppression of tumorigenicity in human cell hybrids derived from cell lines expressing different activated ras
A G Geiser1, M J Anderson, E J Stanbridge
1Department of Microbiology and Molecular Genetics, University of California, Irvine 92717.
Abstract:
Four different human tissue-derived cell lines, each previously shown to express either a Ha-, Ki-, or N-ras-activated oncogene, were fused in four different paired combinations. The three combinations that involved the tumor line HT1080 (activated N-ras oncogene) were found to be tumorigenic in nude mice, but to different degrees. However, the fusion of the tumor lines EJ and SW480 (activated Ha-ras and Ki-ras, respectively) resulted in hybrid cells suppressed for tumorigenicity. The EJ x SW480 hybrids were found to harbor and express both of the activated ras oncogenes. The results suggest that tumorigenic suppression can occur in the presence of two transforming oncogenes of the ras family and that tumorigenicity associated with ras oncogene activation involves additional mechanisms that may differ among tumor cells.
Insights
Cell fusion experiments reveal that combining tumor cells with activated ras oncogenes can suppress tumorigenicity. This suggests complex mechanisms beyond single ras oncogene activation drive tumor formation.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Ras oncogenes (Ha-, Ki-, N-ras) are frequently activated in human cancers.
- The role of specific ras oncogene combinations in tumorigenicity is not fully understood.
Purpose of the Study:
- To investigate the effect of fusing human tumor cell lines with different activated ras oncogenes on tumorigenicity.
- To explore the interplay between multiple ras oncogenes in cancer development.
Main Methods:
- Fusion of four human tissue-derived cell lines expressing activated Ha-, Ki-, or N-ras oncogenes in paired combinations.
- Assessment of tumorigenicity of resulting hybrid cell lines in nude mice.
Main Results:
- Hybrid cells involving HT1080 (N-ras) were tumorigenic to varying degrees.
- Fusion of EJ (Ha-ras) and SW480 (Ki-ras) tumor lines resulted in hybrid cells with suppressed tumorigenicity.
- EJ x SW480 hybrids expressed both activated Ha-ras and Ki-ras oncogenes.
Conclusions:
- Tumorigenic suppression can occur even with the presence of two activated ras oncogenes.
- Ras oncogene activation's role in tumorigenicity involves additional, potentially variable, mechanisms across different tumor cells.