Oncogenes and anti-oncogenes: Their role in the genesis and progression of tumors

Abstract

Recently, molecular genetic analyses have revealed that the genesis and progression of tumors are the results of accumulated changes in two major classes of growth regulatory genes: the oncogenes and the tumor-suppressor genes. Most of these genes belong to an intra cellular signal transduction pathway or to cell cycle regulators. Several sequential genetic alterations, i.e., the hyperactivation of growth promoting genes and the inactivation of growth inhibiting genes, appear to be required to direct cells toward the malignant phenotype. In this regard, the genomic instability that is induced by the mutations of genes important for cell-cycle regulation and DNA repair, such as the p53 and p16 genes, leads to the next multiple gene alterations. Gene amplification, point mutation, insertion, translocation, and rearrangement are the major mechanisms of oncogene activation. In brain tumors, alterations of the erbB 1 gene encoding EGF receptor have been frequently reported. Other oncogene amplifications such as sis, c myc, and PDGF-R have also been reported. Further, inactivation of many tumor suppressor genes, including the p53, NF1, NF2, and the p16 genes, and the VHL gene in cases of the von Hippel Lindau disease, have been proved in brain tumors. In this paper, the functional role of some tumor suppressor genes is discussed. Basic ongoing research of these oncogenes and tumor suppressor genes may soon contribute to a breakthrough and the development of new technological methods for brain tumor treatment.