A novel human prostate-specific, androgen-regulated homeobox gene (NKX3.1) that maps to 8p21, a region frequently deleted in prostate cancer.
We have isolated a prostate-specific gene (NKX3.1) in humans that is homologous to the Drosophila NK homeobox gene family. Northern blot analyses indicate that this gene is expressed at high levels in adult prostate and at a much lower level in testis, but is expressed little or not at all in several other tissues. In an androgen-dependent prostate carcinoma line, LNCaP, NKX3.1 mRNA is expressed at a basal level that was increased markedly upon androgen stimulation; the NKX3.1 mRNA was undetectable in several other human tumor cell lines including two androgen-independent prostate carcinoma lines. The NKX3.1 gene maps to chromosome band 8p21, a region frequently reported to undergo a loss of heterozygosity associated with tissue dedifferentiation and loss of androgen responsiveness during the progression of prostate cancer. Based on these data we propose that NKX3.1 is a candidate gene for playing a role in the opposing processes of androgen-driven differentiation of prostatic tissue and loss of that differentiation during the progression of prostate cancer.
He
W W
WW
Department of Molecular Biology, Human Genome Sciences Inc., Rockville, Maryland 20850, USA.
Sciavolino
P J
PJ
Wing
J
J
Augustus
M
M
Hudson
P
P
Meissner
P S
PS
Curtis
R T
RT
Shell
B K
BK
Bostwick
D G
DG
Tindall
D J
DJ
Gelmann
E P
EP
Abate-Shen
C
C
Carter
K C
KC
D000328:Adult; D000595:Amino Acid Sequence; D000728:Androgens / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004330:Drosophila / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D005801:Genes, Homeobox; D017344:Genes, Insect; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism; D011467:Prostate / Q000254:growth & development / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000728:Androgens; D018398:Homeodomain Proteins; C491178:NKX3-1 protein, human; C102837:Nkx3-1 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; D004247:DNA