Important note: Information in this article was accurate in 1985. The state of the art may have changed since the publication date.
TRANSFORMING GENES OF RETROVIRUSES AND HUMAN TUMOR CELLS (MEETING ABSTRACT)
Lymphokine Res; 3(2):62 1984. Unique Identifier : AIDSLINE ICDB/85604703 Aaronson SA; Lab. of Celular and Molecular Biology, Nat. Cancer Inst.,; Bethesda, MD 20205
Abstract:
Investigations of the genetic alterations that cause normal cells to become malignant have focused on a small set of cellular genes. Acute transforming retroviruses have substituted viral genes necessary for replication with these discrete segments of host genetic information. When incorporated within the retroviral genome, these transduced cellular sequences, termed onc genes, acquire the ability to induce neoplastic transformation. Proto-oncogenes can also be activated to become transforming genes by mechanisms independent of retrovirus involvement. Genetic changes as small as point mutations, as well as DNA rearrangements such as transpositions and chromosomal translocations, have all been implicated in this process. By use of the NIH/3T3 transfection assay, we have demonstrated the frequent activation of members of the ras family of proto-oncogenesis in human tumors. K-ras, H-ras, or N-ras transforming genes are activated in as many as 50% of individual tumors analyzed from specific forms of human cancer. While the presence of such oncogenes does not appear to be specific to a particular cell type or stage of differentiation, N-ras seems to be preferentially activated in human hematopoietic tumors. Findings that all cells within the same tumor contain the transforming gene, as well as the lack of detection of the activated gene in normal cells from the same patient, imply that activation of the transforming gene may be intimately connected with processes leading to malignancy. Genetic lesions responsible for activation of ras genes have been localized to point mutations either at amino acid position 12 or 61. Efforts aimed at analyzing the biologic activity of ras-related human oncogenes in cells other than NIH/3T3 cells will be discussed. Very recent findings have provided the first direct link between an onc gene and a known biologic function. The simian sarcoma virus (SSV) onc gene, v-sis, has been sequenced and its 28,000 dalton product, p28sis, identified by means of antisera prepared against small peptides derived from sequence analysis of v-sis. Studies on human platelet-derived growth factor (PDGF), a potent mitogen for cells of connective tissue origin, have led to the elucidation of its amino terminal amino acid sequence. Computer comparisons of this protein sequence with the predicted amino acid sequence of p28sis has revealed an extraordinary degree of homology. Additional data on the amino acid sequence of PDGF has further strengthened this correspondence, implying that the two proteins have arisen from the same or closely related cellular genes. We demonstrate that p28sis is processed in vivo in a manner closely approximating that of PDGF. Other structural and functional relationships of the two proteins will be presented as well as evidence associating the specific expression of the sis gene in human cancers which are targets for the growth promoting actions of human PDGF.
Keywords: Amino Acid Sequence *Cell Transformation, Neoplastic *Cell Transformation, Viral Comparative Study *Genes, Viral Human *Oncogenes Peptides/ANALYSIS Platelet-Derived Growth Factor/ANALYSIS Protein Conformation Retroviridae/*GENETICS Sarcoma Viruses, Simian/ANALYSIS Viral Proteins/ANALYSIS MEETING PAPER
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Important note: Information in this article was accurate in 1985. The state of the art may have changed since the publication date.
