Mol. Hum. Reprod. Advance Access originally published online on June 8, 2009
Molecular Human Reproduction 2009 15(8):479-488; doi:10.1093/molehr/gap040
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The pluripotency transcription factor Krüppel-like factor 4 is strongly expressed in intratubular germ cell neoplasia unclassified and seminoma
1Department of Animal Science, McGill University, Macdonald Campus, 21111 Lakeshore Road, Ste-Anne-de-Bellevue, QC, Canada H9X 3V9 2 Institute of Anatomy, Hufelandstrasse 55, University of Duisburg-Essen Medical School, 45147 Essen, Germany 3Department of Stem Cell Biology, German Primate Center, Leibniz Institute for Primate Research, Kellnerweg 4, 37077 Göttingen, Germany 4Department of Pathology, University of Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany 5 Institute of Veterinary Anatomy, Histology and Embryology, University of Giessen, Frankfurter Strasse 98, 35392 Giessen, Germany 6Department of Cancer Prevention, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Center for Cancer Biomedicine, University of Oslo, Oslo, Norway
7 Correspondence address. Tel: +49 551-3851-132; Fax: +49 551-3851-288; E-mail: rbehr{at}dpz.eu
Germ cell tumors of the testis are the most frequent tumors in men between 20 and 40 years. Their most common subtype is the seminoma, which arises like the embryonal carcinoma from an intratubular germ cell neoplasia unclassified (IGCNU), i.e. fetal germ cells that escaped from the control of the developing testicular stem cell niche, eventually leading to a fully developed seminoma (or embryonal carcinoma). The molecular causes for the development of an IGCNU are still unknown. However, IGCNU cells share the expression of several factors with primordial germ cells and gonocytes and, interestingly, also with pluripotent embryonic stem (ES) cells and induced pluripotent stem (iPS) cells. One factor playing important roles in both iPS and ES cells is the transcription factor Krüppel-like factor 4 (KLF4). This study examined KLF4 expression data from 179 human testicular samples including normal controls and seminoma, deposited in Gene Expression Omnibus repository for microarray data at the National Centre for Biotechnology Information. Immunohistochemistry was used to detect KLF4 protein expression in IGCNU (n = 6), seminoma (n = 14) and fetal human testes (n = 14). Microarray data from three independent sources suggest higher mRNA expression in seminoma than in normal testis. Normal spermatogonia, which are the stem cells of spermatogenesis, controlled by their stem cell niche, do not express KLF4. In contrast, IGCNU and seminoma cells strongly express KLF4. In conclusion, this finding suggests that KLF4 may be an important factor for the maintenance of the developmental and the tumorigenic potential of IGCNU as well as for the malignancy of seminoma.
Key words: Krüppel-like factor 4/germ cell/gonocyte/intratubular germ cell neoplasia unclassified/seminoma
Submitted on January 27, 2009; resubmitted on May 7, 2009; accepted on May 28, 2009.