ACTIVATION OF A GENE CODING FOR A NORMAL HUMAN GROWTH FACTOR TO ONE WITH TRANSFORMING PROPERTIES

Important note: Information in this article was accurate in 1986. The state of the art may have changed since the publication date.

ACTIVATION OF A GENE CODING FOR A NORMAL HUMAN GROWTH FACTOR TO ONE WITH TRANSFORMING PROPERTIES

Dev Oncol; 28:54-66 1985. Unique Identifier : AIDSLINE ICDB/86621725
Aaronson SA; Robbins KC; NCI, Building 37, Room 1A07, Bethesda, MD 20205

Abstract: Investigations of the characteristics of the sis oncogene, originally isolated from simian sarcoma virus (SSV), are reviewed. The results of analyses to determine the nucleotide sequence, identify the SSV transforming protein, and characterize the relationship between the SSV transforming protein and human platelet-derived growth factor (PDGF) are described. In studies of the human sis locus, v-sis-related sequences were isolated from a bacteriophage library of normal human DNA. Five v-sis-homologous restriction fragments were identified that could be localized within a 15 kilo base-pair (kbp) region. C-sis (human), like v-sis, represents an incomplete gene. When the predicted c-sis coding sequence was compared with that of known PDGF-2 peptides, almost complete homology was observed, confirming that the c-sis (human) was the structural gene for PDGF-2. Activation of the human c-sis/PDGF-2 sequence required two in vitro manipulations, neither of which was sufficient alone: (1) placement of human c-sis under the control of a retroviral long terminal repeat (LTR), which led to transcription, but not synthesis, of detectable c-sis-related translation products; and (2) addition of LTR to a putative upstream exon in a c-sis flanking genomic DNA clone isolated from a normal human library, which led to acquisition of high titered transforming activity comparable to that of SSV DNA. PDGF-2 gene products were expressed in such transformants. Normal PDGF-2 expressed in NIH/3T3 cells appears to be sufficient to induce transformation. (40 Refs)

Keywords: Animal Base Sequence Cell Line *Cell Transformation, Neoplastic DNA, Viral/GENETICS Gene Expression Regulation Genes, Viral *Genetic Code Human Mice *Oncogenes Peptides/*GENETICS Platelet-Derived Growth Factor/GENETICS *Proto-Oncogenes Sarcoma Viruses, Simian/GENETICS Somatotropin/*GENETICS Viral Proteins/GENETICS MEETING PAPER

861130
M86B0254

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