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.
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.
Palumbo
Camilla
C
Department of Cell Biology, University of Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands.
van Roozendaal
Kees
K
Gillis
Ad J
AJ
van Gurp
Ruud H
RH
de Munnik
Hannie
H
Oosterhuis
J Wolter
JW
van Zoelen
E Joop
EJ
Looijenga
Leendert H
LH
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
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