Analysis of androgen regulated homeobox gene NKX3.1 during prostate carcinogenesis.
OBJECTIVE
NKX3.1 is an androgen regulated gene that is largely specific to the prostate for expression and it is predicted to encode a homeobox protein. Null alleles of NKX3.1 in mice results in impaired prostate development as well as hyperplasia and dysplasia of the prostate. In addition, the NKX3.1 gene maps to a region of high loss of heterozygosity in prostate cancer in humans, suggesting that NKX3.1 might have a direct role in prostate carcinogenesis, possibly functioning as a tumor suppressor protein. Previous studies of the levels of NKX3.1 mRNA or protein in prostate cancer specimens have resulted in conflicting findings.


METHODS
To resolve this issue we assessed NKX3.1 expression by mRNA in situ analysis and immunohistochemistry on the same prostate cancer tissue arrays.


RESULTS
Data showed that NKX3.1 mRNA and protein levels in prostate cancer specimens are correlated, suggesting that most regulation is at the transcriptional level. There was no correlation of NKX3.1 expression levels with tumor grade or clinical stage. In general there was a suggestion that worse clinical features at surgery were associated with lower IHC stain scores. In particular, extracapsular extension but not seminal vesicle invasion inversely correlated with NKX3.1 expression.


CONCLUSIONS
Together these data suggest that NKX3.1 does not function as a typical tumor suppressor protein in prostate cancer but it may still have important regulatory roles during prostate cancer progression.
Department of Molecular Biosciences, and Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway.
Ceren G
CG
Korkmaz
Kemal S
KS
Korkmaz
Judith
J
Manola
Zhijun
Z
Xi
Bjørn
B
Risberg
Håvard
H
Danielsen
Janet
J
Kung
William R
WR
Sellers
Massimo
M
Loda
Fahri
F
Saatcioglu
D000328:Adult; D000368:Aged; D000728:Androgens / Q000235:genetics*; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D005801:Genes, Homeobox; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis
D000728:Androgens; D012333:RNA, Messenger