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Noncoordinate expression of SV40-induced transformation and tumorigenicity in mouse cell hybrids
Abstract:
Somatic mouse cells hybrids formed by fusion of nontumorigenic 3T3 closely related SV40-transformed SVT2 cells were analyzed in a study designed to probe the genetic basis of the multiple phenotypic changes induced by SV40 transformation. These hybrids showed noncoordinate expression of the transformation phenotype. Although they cloned at high efficiency in medium with low serum and expressed the SV40 T-antigen of the SVT2 parent, hybrid cells grew poorly without anchorage and exhibited a cell and colony morphology intermediate between that of the parents. Tumorigenicity was assayed quantitatively by subcutaneous coinjection into athymic nude mice of serial dilutions of 10(2) to 10(5) hybrid cells with 10(7) lethally irradiated 3T3 cells. The results showed that 100--1000 times more hybrid cells had to be injected for tumor formation than were required with SVT2. These and other observations show that most 3T3/SVT2 hybrid cells are not tumorigenic but that each population contains a rare subset of tumorigenic cells.
Insights
Hybrid cells from fusing normal and SV40-transformed mouse cells showed mixed traits. Most hybrids were not tumorigenic, but rare tumorigenic cells were found within each population.
Area of Science:
- Cell biology
- Cancer research
- Genetics
Background:
- Simian virus 40 (SV40) transformation induces significant phenotypic changes in cells.
- Understanding the genetic basis of these changes is crucial for cancer research.
Purpose of the Study:
- To investigate the genetic mechanisms underlying SV40-induced phenotypic alterations.
- To analyze the expression of the transformation phenotype in somatic cell hybrids.
Main Methods:
- Fusion of nontumorigenic 3T3 cells with SV40-transformed SVT2 cells to create hybrids.
- Analysis of hybrid cell cloning efficiency, anchorage independence, morphology, and SV40 T-antigen expression.
- Quantitative assay of tumorigenicity via subcutaneous coinjection into athymic nude mice.
Main Results:
- Hybrid cells displayed noncoordinate expression of the transformation phenotype.
- While hybrids efficiently cloned in low serum and expressed SV40 T-antigen, they showed poor anchorage-independent growth and intermediate morphology.
- Tumorigenicity assays revealed that 100-1000 times more hybrid cells were required for tumor formation compared to SVT2 cells.
Conclusions:
- Most 3T3/SVT2 hybrid cells are not tumorigenic, indicating suppression of tumorigenicity.
- Each hybrid cell population contains a rare subset of tumorigenic cells, suggesting genetic instability or the presence of specific oncogenic drivers.