title: Expression of the PDGF alpha-receptor 1.5 kb transcript, OCT-4, and c-KIT in human normal and malignant tissues. Implications for the early diagnosis of testicular germ cell tumours and for our understanding of regulatory mechanisms.
abstract: Human testicular germ cell tumours of adolescents and adults (TGCTs), including their precursor lesion carcinoma in situ (CIS), show expression of a 1.5 kb alternative transcript of the platelet-derived growth factor (PDGF) alpha-receptor gene. The so-called P2 promoter involved is located in intron 12 and its activity was found to be mutually exclusive with activity of the classical promoter (P1), which encodes the full-length receptor. The presence of the 1.5 kb transcript could be a putative marker for the early molecular diagnosis of TGCTs. In order to validate the RT-PCR approach, this study shows that not more than 100 transcripts are necessary to obtain positivity in the test used; moreover, samples from TGCTs or CIS-containing tissues can be diluted many-fold before resulting in false-negative findings. This study also shows that within TGCTs, as in TGCT-derived cell lines, expression of the 1.5 kb transcript is differentiation-dependent and positively correlated with expression of the embryonic transcription factor OCT-4/POU5F1. Furthermore, the results indicate that in some non-TGCT cancers and cell lines the 1.5 kb transcript is also expressed, but without concomitant OCT-4/POU5F1 expression. The 1.5 kb transcript is also present in early B cells and derived leukaemias (B-ALL). In spite of similarities in chromosomal location, down-regulation upon differentiation of TGCTs, and PDGF alpha-receptor and c-KIT (the stem cell factor receptor) both being a tyrosine kinase receptor, no correlation was found between activity of the P2 promoter of the PDGF alpha-receptor gene and expression of c-KIT. In conclusion, the 1.5 kb transcript of the PDGF alpha-receptor is expressed in various cells and tissues, including particular blood cells. Although this may hamper the use of this transcript as a marker for malignancies in general, it does not appear to interfere with assays for the early detection of TGCTs.
authors.affiliation: Department of Cell Biology, University of Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands.
authors.forename: Camilla
authors.initials: C
authors.lastname: Palumbo
authors.forename: Kees
authors.initials: K
authors.lastname: van Roozendaal
authors.forename: Ad J
authors.initials: AJ
authors.lastname: Gillis
authors.forename: Ruud H
authors.initials: RH
authors.lastname: van Gurp
authors.forename: Hannie
authors.initials: H
authors.lastname: de Munnik
authors.forename: J Wolter
authors.initials: JW
authors.lastname: Oosterhuis
authors.forename: E Joop
authors.initials: EJ
authors.lastname: van Zoelen
authors.forename: Leendert H
authors.initials: LH
authors.lastname: Looijenga
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000378:metabolism; D006801:Humans; D008297:Male; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009373:Neoplasms, Germ Cell and Embryonal / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D050814:Octamer Transcription Factor-3; D016133:Polymerase Chain Reaction / Q000379:methods; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D012878:Skin Neoplasms / Q000378:metabolism; D013736:Testicular Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D014157:Transcription Factors; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha