AIMS: NANOG is a key regulator of embryonic stem cell (ESC) self-renewal and pluripotency. Our recent genome-wide gene expression profiling study of the precursor of testicular germ cell tumours, carcinoma in situ testis (CIS), showed close similarity between ESC and CIS, including high NANOG expression. In the present study we analysed the protein expression of NANOG during normal development of human testis and in a large series of neoplastic/dysgenetic specimens. METHODS AND RESULTS: We detected abundant expression of NANOG in CIS and in CIS-derived testicular tumours with marked differences; seminoma and embryonal carcinoma were strongly positive, differentiated somatic elements of teratoma were negative. We provide evidence for the fetal origin of testicular cancer as we detected strong expression of NANOG in fetal gonocytes up to gestational week 20, with subsequent down-regulation occurring earlier than for OCT-4. We detected no expression at the protein level in normal testis. CONCLUSIONS: NANOG is a new marker for testicular CIS and germ cell tumours and the high level of NANOG along with OCT-4 are determinants of the stem cell-like pluripotency of the preinvasive CIS cell. Timing of NANOG down-regulation in fetal gonocytes suggests that NANOG may act as a regulatory factor up-stream to OCT-4.
AIMS: NANOG is a key regulator of embryonic stem cell (ESC) self-renewal and pluripotency. Our recent genome-wide gene expression profiling study of the precursor of testicular germ cell tumours, carcinoma in situ testis (CIS), showed close similarity between ESC and CIS, including high NANOG expression. In the present study we analysed the protein expression of NANOG during normal development of human testis and in a large series of neoplastic/dysgenetic specimens. METHODS AND RESULTS: We detected abundant expression of NANOG in CIS and in CIS-derived testicular tumours with marked differences; seminoma and embryonal carcinoma were strongly positive, differentiated somatic elements of teratoma were negative. We provide evidence for the fetal origin of testicular cancer as we detected strong expression of NANOG in fetal gonocytes up to gestational week 20, with subsequent down-regulation occurring earlier than for OCT-4. We detected no expression at the protein level in normal testis. CONCLUSIONS:NANOG is a new marker for testicular CIS and germ cell tumours and the high level of NANOG along with OCT-4 are determinants of the stem cell-like pluripotency of the preinvasive CIS cell. Timing of NANOG down-regulation in fetal gonocytes suggests that NANOG may act as a regulatory factor up-stream to OCT-4.
Authors: Si Brask Sonne; Amy S Herlihy; Christina E Hoei-Hansen; John E Nielsen; Kristian Almstrup; Niels E Skakkebaek; Alexander Marks; Henrik Leffers; Ewa Rajpert-De Meyts Journal: Virchows Arch Date: 2006-05-31 Impact factor: 4.064
Authors: Ewart W Kuijk; Jeffrey de Gier; Susana M Chuva de Sousa Lopes; Ian Chambers; Ans M M van Pelt; Ben Colenbrander; Bernard A J Roelen Journal: PLoS One Date: 2010-06-07 Impact factor: 3.240
Authors: Si Brask Sonne; Kristian Almstrup; Marlene Dalgaard; Agnieszka Sierakowska Juncker; Daniel Edsgard; Ludmila Ruban; Neil J Harrison; Christian Schwager; Amir Abdollahi; Peter E Huber; Søren Brunak; Lise Mette Gjerdrum; Harry D Moore; Peter W Andrews; Niels E Skakkebaek; Ewa Rajpert-De Meyts; Henrik Leffers Journal: Cancer Res Date: 2009-06-02 Impact factor: 12.701
Authors: Anthony D Krentz; Mark W Murphy; Teng Zhang; Aaron L Sarver; Sanjay Jain; Michael D Griswold; Vivian J Bardwell; David Zarkower Journal: Dev Biol Date: 2013-03-06 Impact factor: 3.582