Expression of the normal human sis/PDGF-2 coding sequence induces cellular transformation.
The human sis proto-oncogene contains the coding sequence for one of two polypeptide chains present in preparations of biologically active human platelet-derived growth factor (PDGF). A human clone, c-sis clone 8, which contains all of the v-sis-related sequences present in human DNA, was transcriptionally inactive when transfected into NIH/3T3 cells. When placed under the control of a retrovirus LTR, the clone was transcribed at levels comparable to that observed in cells transformed by SSV DNA. However, c-sis clone 8 DNA did not express detectable sis/PDGF-2 proteins and lacked biologic activity. A putative upstream exon was identified by its ability to detect the 4.2 kb sis-related transcript in certain human cells. When this sequence was inserted in the proper orientation between the LTR and c-sis clone 8, the chimeric molecule acquired high titered transforming activity, comparable to that of SSV DNA. Transformants containing this construct expressed human sis/PDGF-2 translational products. Thus the normal coding sequence for a human growth factor has transforming activity when expressed in an appropriate assay cell.
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004262:DNA Restriction Enzymes; D005796:Genes; D005910:Glioma; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D009857:Oncogenes; D010957:Plasmids; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D012190:Retroviridae / Q000235:genetics*; D012842:Sarcoma Virus, Woolly Monkey / Q000235:genetics*; D014162:Transfection
C000715470:MAS1 protein, human; D010982:Platelet-Derived Growth Factor; D000090063:Proto-Oncogene Mas; D004262:DNA Restriction Enzymes