Onco-suppressor genes and their involvement in cancer (review).

Onco-suppressor genes are a heterogeneous set of genes that inhibit the cancer-related phenotype of cells. Because they are difficult to identify, only a few have been described. Evidence for their existence has mainly been indirect and comes from the following types of study. 1. Recessive cancer genes in higher and lower eukaryotes have been detected. If both alleles of these genes are deleted or inactivated, cancer develops. 2. Studies on cell hybrids have implicated genes which suppress various stages in the malignant conversion of normal cells e.g. immortalisation, morphological conversion and metastasis. 3. The isolation from virally induced transformants of flat, non-tumorigenic revertants in which expression of the transforming gene is not down-regulated suggests the presence of genes which suppress the effects of transformation. 4. Blocks to differentiation can be bypassed by inducing compounds or differentiation factors. 5. Studies on tumor inhibitory factors such as tumour necrosis factor and beta-TGF show that they have different effects on different types of cell-acting to promote growth in some cases and inhibit it in others. 6. The discovery of cis-acting negatice regulatory elements suggests that interaction of such elements with proteins may be important for control of gene expression particularly of infecting oncogenic viruses. 7. Suppression of the transformed phenotype of malignant cells by contact with normal cells that controls growth of neighboring cells. 8. The inhibition of proliferation of transformed cells by transfection with DNA from normal cells may be a useful method for cloning onco-suppressor genes. We discuss what is known and what is not known about this important class of gene.