Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours.
OBJECTIVE
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.


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.
University Department of Growth & Reproduction and Department of Pathology, Rigshospitalet, Copenhagen, Denmark. chh@dadlnet.dk
C E
CE
Hoei-Hansen
K
K
Almstrup
J E
JE
Nielsen
S
S
Brask Sonne
N
N
Graem
N E
NE
Skakkebaek
H
H
Leffers
E
E
Rajpert-De Meyts
D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase; D002278:Carcinoma in Situ / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics; D005333:Fetus; D058851:GPI-Linked Proteins; D015972:Gene Expression Regulation, Neoplastic; D018237:Germinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005865:Gestational Age; D018398:Homeodomain Proteins / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000032:analysis; D008297:Male; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013736:Testicular Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000032:analysis
D004268:DNA-Binding Proteins; D058851:GPI-Linked Proteins; D018398:Homeodomain Proteins; D007527:Isoenzymes; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D012333:RNA, Messenger; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D000469:Alkaline Phosphatase; C019839:alkaline phosphatase, placental