The loss of NKX3.1 expression in testicular--and prostate--cancers is not caused by promoter hypermethylation.
BACKGROUND
Recent studies have demonstrated that the NKX3.1 protein is commonly down-regulated in testicular germ cell tumors (TGCTs) and prostate carcinomas. The homeobox gene NKX3.1 maps to chromosome band 8p21, which is a region frequently lost in prostate cancer, but not in TGCT. Mutations have not been reported in the NKX3.1 sequence, and the gene is hypothesized to be epigenetically inactivated. In the present study we examined the methylation status of the NKX3.1 promoter in relevant primary tumors and cell lines: primary TGCTs (n = 55), intratubular germ cell neoplasias (n = 7), germ cell tumor cell lines (n = 3), primary prostate adenocarcinomas (n = 20), and prostate cancer cell lines (n = 3) by methylation-specific PCR and bisulphite sequencing.


CONCLUSIONS
Down-regulation of NKX3.1 expression was generally not caused by promoter hypermethylation, which was only found in one TGCT. However, other epigenetic mechanisms, such as modulation of chromatin structure or modifications of histones, may explain the lack of NKX3.1 expression, which is seen in most TGCTs and prostate cancer specimens.
Lind
Guro E
GE
Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, 0310 Oslo, Norway. guroli@ulrik.uio.no
Skotheim
Rolf I
RI
Fraga
Mario F
MF
Abeler
Vera M
VM
Henrique
Rui
R
Saatcioglu
Fahri
F
Esteller
Manel
M
Teixeira
Manuel R
MR
Lothe
Ragnhild A
RA
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D019175:DNA Methylation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D018237:Germinoma / Q000235:genetics* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D013736:Testicular Neoplasms / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D018398:Homeodomain Proteins; C491178:NKX3-1 protein, human; D014157:Transcription Factors