THE REP68 PROTEIN OF ADENOASSOCIATED VIRUS TYPE-2 STIMULATES EXPRESSION OF THE PLATELET-DERIVED GROWTH-FACTOR-B C-SIS PROTOONCOGENE

Rep68 protein, encoded by adeno-associated virus type 2 (AAV), has bee n previously shown to bind to specific sequences within the viral geno me and in human chromosome 19. The effect of AAV Rep protein on human cellular genes is of interest because AAV is being developed as a gene therapy vector. We have identified sequences related to the Rep recog nition sequence in the AAV P-5 promoter in or near the c-sis proto-onc ogene and the genes coding for a hepatocyte glucose transporter, alpha -A-crystallin, and carcinoma marker GA733-1, The ability of Rep68 to b ind to these sites was established by gel shift assays, and the effect of Rep68 on the expression of these genes was tested by semiquantitat ive reverse transcriptase PCR, Rep68 enhances the expression of the ca is proto-oncogene, which codes for the B polypeptide of platelet-deriv ed growth factor, a multifunctional growth factor that is involved in embryonic development, tissue regeneration, osteogenesis, fibrosis, at herosclerosis, and neoplasia.