PDGF B mRNA variants in human tumors with similarity to the v-sis oncogene: Expression of cellular PDGF B protein is associated with exon 1 divergence, but not with a 3 ' UTR splice variant

While platelet-derived growth factor, PDGF, is not regularly expressed in m esenchymal tissues, PDGF B mRNA is often found in tumors derived from these tissues. PDGF B protein is also present, but the protein levels in individ ual tumors do not appear to correlate well with those of the mRNA. PDGF B i s homologous to the v-sis oncogene of simian sarcoma virus (SSV), and certa in deletions confined to 3' and 5' non coding sequences of PDGF B mRNA are consistently found in tumors induced by SSV and by a PDGF B retrovirus. Par t of exon 1, including a non-coding GC-rich regulatory domain and the signa l sequence as well as a 149 nucleotide long AU-rich stretch in the 3' non-c oding region, are often lost. We hoped that this information could provide a clue to defective regulatory mechanisms present in human tumors and have searched for such mRNA variants in human sarcoma cell lines and soft tissue tumors. We identified a splice variant of PDGF B mRNA that, similar to v-s is, lacks the 149 nucleotide stretch and introduces an anomalous splice poi nt between exons 6 and 7. This weakly abundant mRNA variant was co-expresse d with the regular PDGF B mRNA, but its presence failed to show any associa tion with increased levels of immunohistochemically detectable PDGF B prote in. Instead, the highest levels of cellular PDGF B protein were found in sa mples with mRNAs showing exon 1 divergence. The changes in the 5' end of th e mRNA were not accompanied by any genomic aberrations. Int. J. Cancer 85:2 11-222, 2000. (C) 2000 Wiley-Liss, Inc.