NKX3.1 expression is lost in testicular germ cell tumors.
NKX3.1 is a homeobox gene which exhibits prostate and testis specific expression. Loss of NKX3.1 expression has been implicated in prostate development and tumorigenesis, but the role of NKX3.1 in testis biology is not known. Here we show that NKX3.1 expression is dramatically down-regulated in testicular cancer of germ cell origin. Immunohistochemical analysis on a tissue microarray containing 510 testicular tissue samples indicate that NKX3.1 is expressed at high levels in normal germ cells and in carcinoma in situ, but is sharply decreased or absent in most seminomas and all embryonal carcinomas. However, NKX3.1 is expressed in a subset of the more differentiated nonseminomas. We provide evidence that these changes in NKX3.1 protein levels are mainly due to transcriptional effects. These results suggest that NKX3.1 is essential for normal testis function and that its loss of expression is highly associated with the invasive phenotype of testicular germ cell tumors.
Skotheim
Rolf I
RI
Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital and University of Oslo, Oslo, Norway.
Korkmaz
Kemal S
KS
Klokk
Tove I
TI
Abeler
Vera M
VM
Korkmaz
Ceren G
CG
Nesland
Jahn M
JM
Fosså
Sophie D
SD
Lothe
Ragnhild A
RA
Saatcioglu
Fahri
F
D018237:Germinoma / Q000378:metabolism* / Q000556:secondary; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013736:Testicular Neoplasms / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
D018398:Homeodomain Proteins; C491178:NKX3-1 protein, human; D012333:RNA, Messenger; D014157:Transcription Factors