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

Abstract

While platelet-derived growth factor, PDGF, is not regularly expressed in mesenchymal tissues, PDGF B mRNA is often found in tumors derived from these tissues. PDGF B protein is also present, but the protein levels in individual tumors do not appear to correlate well with those of the mRNA. PDGF B is homologous to the v-sis oncogene of simian sarcoma virus (SSV), and certain 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. Part of exon 1, including a non-coding GC-rich regulatory domain and the signal sequence as well as a 149 nucleotide long AU-rich stretch in the 3; non-coding 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-sis, lacks the 149 nucleotide stretch and introduces an anomalous splice point between exons 6 and 7. This weakly abundant mRNA variant was co-expressed with the regular PDGF B mRNA, but its presence failed to show any association with increased levels of immunohistochemically detectable PDGF B protein. Instead, the highest levels of cellular PDGF B protein were found in samples with mRNAs showing exon 1 divergence. The changes in the 5; end of the mRNA were not accompanied by any genomic aberrations.