¹Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan 48201

²Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan 48201

³Stehlin Foundation for Cancer Research, Houston, Texas 77003, USA

^aAuthor for correspondence

We have previously shown that noninfected human T-cell lines express the canonical 5.7 kb mRNA coding for the type platelet-derived growth factor-receptor (PDGF -receptor), whereas HTLV-I-infected T-cell lines express a novel PDGF -receptor mRNA of 3.8 kb. In this report, we have extended those studies to molecularly characterize the 3.8 kb PDGF -receptor mRNA and show that it has resulted from integration of an apparently undeleted HTLV-I provirus into the PDGF -receptor gene in an orientation enabling expression of a truncated PDGF -receptor mRNA using the 3' HTLV-I long terminal repeat as a promoter. Further, NIH3T3 cells transfected with a plasmid containing the truncated PDGF -receptor ORF plasmid generate colonies in soft agar with more cells per colony than untransfected cells, or cells transfected with the Tax 1 or PDGF-B (c-sis) plasmids. These results indicate that the truncated PDGF -receptor protein acquires transforming capability and that HTLV-I-induced truncation of PDGF -receptor may correlate with HTLV-I-associated neoplasia of human T-cells.

receptor tyrosine kinase; PDGF; insertional mutagenesis; HTLV-I; long terminal repeat; T-lymphocyte