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

Camilla Palumbo, Kees van Roozendaal, Ad J Gillis, Ruud H van Gurp, Hannie de Munnik, J Wolter Oosterhuis, E Joop van Zoelen, Leendert H Looijenga

Research output: Contribution to journalArticlepeer-review

81 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)467-77
Number of pages11
JournalThe Journal of pathology
Volume196
Issue number4
DOIs
Publication statusPublished - Apr 2002
Externally publishedYes

Keywords

  • Adolescent
  • Adult
  • Biomarkers, Tumor/metabolism
  • DNA-Binding Proteins/metabolism
  • Gene Expression Regulation, Neoplastic
  • Glioma/metabolism
  • Humans
  • Male
  • Melanocytes/metabolism
  • Melanoma/metabolism
  • Neoplasm Proteins/metabolism
  • Neoplasms, Germ Cell and Embryonal/diagnosis
  • Octamer Transcription Factor-3
  • Polymerase Chain Reaction/methods
  • Proto-Oncogene Proteins c-kit/metabolism
  • Receptor, Platelet-Derived Growth Factor alpha/genetics
  • Skin Neoplasms/metabolism
  • Testicular Neoplasms/diagnosis
  • Transcription Factors

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