Developmentally Regulated Expression of Two Novel Platelet-derived Growth Factor α-Receptor Transcripts in Human Teratocarcinoma Cells

Abstract

Two novel platelet-derived growth factor (PDGF) α-receptor transcripts of 1.5 kilobases and 5.0 kilobases are expressed in the human teratocarcinoma cell line Tera-2 only while the cells are in an undifferentiated state. After retinoic acid-induced differentiation, expression of these mRNAs is completely shut off and instead, the cells express a single 6.4-kilobase mRNA species which is also expressed in many other cell types. The 1.5-kilobase mRNA initiates within intron 12, contains the correctly spliced exons 13, 14, 15, and 16, and contains a cryptic exon, designated teratocarcinoma cryptic exon, at the 3′ end. Teratocarcinoma cryptic exon contains a functional polyadenylation signal. Exons 13 to 16 correspond to the first tyrosine kinase domain and to part of the interkinase domain of the PDGF α-receptor. Recently, a splice variant lacking exon 14 was identified. These results show that a combination of alternative promoter usage and alternative splicing of the human PDGF α-receptor gene occur in a developmentally regulated fashion. In vitro translation of the 1.5-kilobase mRNA generates protein products which can be specifically immunoprecipitated with a PDGF α-receptor-specific antibody. The significance of the expression of this transcript for the growth factor-independent proliferation of undifferentiated Tera-2 cells is unclear. Expression of PDGF α-receptor transcripts containing the cryptic exon may be useful as a marker for undifferentiated stem cells in human teratocarcinomas.