Retroviral and human cellular oncogenes.

Unexpected meeting of two separate lines of research resulted in the discovery of oncogenes. Oncogenes are deoxyribonucleic acid (DNA) sequences coding for polypeptide gene products which cause, or contribute to, neoplastic growth of cells. Oncogenes remain almost unchanged through evolution: oncogenes and their gene products of avian, murine, feline, simian and human species show close homology. Retroviruses possess three genes encoding virion structural proteins and envelope. The DNA copy of the viral genome (the provirus) recombines with DNA sequences of the host cell genome and thus acquires an additional DNA sequence of host origin (transduction). The newly acquired DNA sequences render the retrovirus oncogenic. Certain genomic DNA sequences extracted from human tumor cells induce malignant transformation in selected assay systems (transfection). The transforming genes of retroviruses show close homology to these cellular oncogenes. Retroviruses appear to have acquired cellular proto-oncogenes during past interactions with their host cells. In the cell, proto-oncogenes are presumed to fulfill fundamental functions of cell differentiation and mitosis. This is deduced from their preservation during evolution, i.e., proto-oncogenes of avian, lower and higher mammalian and human species display close DNA sequence homology and thus their gene products are also similar in distant species. When expressed in excess or in altered form or at a wrong chromosomal location or at an inappropriate time of the cell cycle, proto-oncogenes function as oncogenes by inducing mitoses and inhibiting differentiation of their host cells.