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Evidence for human DNA-mediated transfer of the suppressed phenotype into malignant Chinese hamster cells
R Schäfer1, A C Nirkko, P M Ambühl
1Division of Cancer Research, Institute of Pathology, University of Zürich, Switzerland.
Abstract:
Genetic suppression of the neoplastic phenotype has been demonstrated in somatic cell hybrids between tumor and normal cells. Suppression in whole-cell and microcell hybrids cannot, as yet, be attributed to specific elements defined at the molecular level. To identify a gene capable of suppressing the neoplastic phenotype, we have introduced DNA of normal human cells into tumorigenic Chinese hamster Wg3-h-o cells. Primary and secondary transfectants which exhibit the suppressed phenotype similar to Wg3-h-o x embryonic fibroblast hybrids were selected. The cells require serum growth factors and anchorage for proliferation in vitro and show a reduced tumorigenicity in nude mice. Transferred human DNA segments were molecularly cloned from a secondary transfectant. Indirect evidence suggests that the cloned human DNA is associated with the expression of the suppressed phenotype.
Insights
Researchers identified a human gene that suppresses cancer cell growth. Introducing normal human DNA into tumor cells reduced their ability to proliferate and form tumors, suggesting a key genetic mechanism for cancer suppression.
Area of Science:
- Cancer research
- Cell biology
- Genetics
Background:
- Genetic suppression of neoplastic phenotype observed in somatic cell hybrids.
- Molecular basis for suppression in whole-cell and microcell hybrids remains undefined.
Purpose of the Study:
- Identify a specific gene responsible for suppressing the neoplastic phenotype.
- Introduce normal human DNA into tumorigenic Chinese hamster cells to isolate suppressor genes.
Main Methods:
- Transfection of tumorigenic Chinese hamster cells (Wg3-h-o) with normal human DNA.
- Selection of primary and secondary transfectants exhibiting suppressed neoplastic phenotype.
- Molecular cloning of transferred human DNA segments from a secondary transfectant.
Main Results:
- Selected transfectants showed suppressed phenotype, requiring serum growth factors and anchorage for in vitro proliferation.
- Transfectants exhibited reduced tumorigenicity in nude mice.
- Cloned human DNA segments from a secondary transfectant showed indirect association with the suppressed phenotype.
Conclusions:
- Successfully introduced and cloned human DNA segments that suppress neoplastic phenotype in hamster tumor cells.
- The cloned human DNA is likely associated with the expression of the suppressed phenotype.
- This study provides a molecular basis for genetic suppression of tumorigenesis.
