Oncogenes and tumor suppressor genes

Proliferation and differentiation of cells are known to be regulated by complicated interactions in which various intracellular molecules are involved. Recent molecular genetic analyses have revealed that the genesis and progression of tumors are the result of accumulated changes in two major classes of growthregulatory genes - the oncogenes and the tumor suppressor genes. Several sequential genetic alterations, especially the inactivation of tumor suppressor genes, appear to allow cells to develop toward a more malignant phenotype. More than 10 tumor suppressor genes have been identified since the retinoblastoma susceptibility gene (RB1) was found as the first suppressor gene of mammalian cells in 1986. These genes can be grouped into four classes according to the functions; genes which are involved in 1) regulation of cell cycle, 2) DNA mismatch repair pathway, 3) cell-cell contact signals, and 4) regulation of ras proto-oncogene product. Especially, genes which encode cell cycle regulatory proteins such as RB1, p53, and p!6 have been found to have frequent mutations in various cancer cells, and these functions are rapidly being characterized. The biochemical characters of these cell cycle regulators will be discussed.