The Transformation-Suppressive Function Is Lost in Tumorgenic Cells and Is Restored upon Transfer of a Suppressor Gene

Abstract

Multiple genetic changes are involved in the conversion of a normal cell into a malignant cell. The nature of genetic alterations in tumor cells has been analyzed by DNA transfection experiments and dominantly acting cellular oncogenes have been identified. The introduction of single activated oncogenes into immortalized cell lines such as mouse NIH/3T3 cells is sufficient for tumorigenic transformation. The requirements for malignant transformation of nonimmortalized, diploid cells are more complex in as much as combinations of oncogenes (e.g. ras and myc genes) or overexpression of single oncogenes and additional genetic alterations are needed (for review see Bishop 1987). Cell-cell fusion experiments have shown that the normal phenotype is restored in somatic cell hybrids of tumorigenic cell lines and normal cells (suppression of malignancy, for review see Klein 1987; Sager 1986; Schäfer 1987). We have demonstrated that rat embryo fibroblasts which have often been used as recipient cells for the introduction of “dominant-acting” oncogenes are still capable of suppressing the neoplastic phenotype when fused with a H-ras transformed rat cell line. The neoplastic phenotype is re-expressed in hybrids which have lost chromosomes (Griegel et al. 1986). These results suggest that a tumor suppressor gene expressed in normal cells is able to counteract the neoplastic transformation induced by a ras gene and that the loss or inactivation of the suppressor gene is a prerequisite for the transforming activity of the oncogene.