PMID- 10215624
OWN - NLM
STAT- MEDLINE
DCOM- 19990601
LR  - 20220408
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 13
IP  - 8
DP  - 1999 Apr 15
TI  - Roles for Nkx3.1 in prostate development and cancer.
PG  - 966-77
AB  - In aging men, the prostate gland becomes hyperproliferative and displays a
      propensity toward carcinoma. Although this hyperproliferative process has been
      proposed to represent an inappropriate reactivation of an embryonic
      differentiation program, the regulatory genes responsible for normal prostate
      development and function are largely undefined. Here we show that the murine
      Nkx3.1 homeobox gene is the earliest known marker of prostate epithelium during
      embryogenesis and is subsequently expressed at all stages of prostate
      differentiation in vivo as well as in tissue recombinants. A null mutation for
      Nkx3.1 obtained by targeted gene disruption results in defects in prostate ductal
      morphogenesis and secretory protein production. Notably, Nkx3.1 mutant mice
      display prostatic epithelial hyperplasia and dysplasia that increases in severity
      with age. This epithelial hyperplasia and dysplasia also occurs in heterozygous
      mice, indicating haploinsufficiency for this phenotype. Because human NKX3.1 is
      known to map to a prostate cancer hot spot, we propose that NKX3.1 is a
      prostate-specific tumor suppressor gene and that loss of a single allele may
      predispose to prostate carcinogenesis. The Nkx3.1 mutant mice provide a unique
      animal model for examining the relationship between normal prostate
      differentiation and early stages of prostate carcinogenesis.
FAU - Bhatia-Gaur, R
AU  - Bhatia-Gaur R
AD  - Center for Advanced Biotechnology and Medicine, University of Medicine and
      Dentistry of New Jersey (UMDNJ)-Robert Wood Johnson Medical School, Piscataway,
      New Jersey 08854 USA.
FAU - Donjacour, A A
AU  - Donjacour AA
FAU - Sciavolino, P J
AU  - Sciavolino PJ
FAU - Kim, M
AU  - Kim M
FAU - Desai, N
AU  - Desai N
FAU - Young, P
AU  - Young P
FAU - Norton, C R
AU  - Norton CR
FAU - Gridley, T
AU  - Gridley T
FAU - Cardiff, R D
AU  - Cardiff RD
FAU - Cunha, G R
AU  - Cunha GR
FAU - Abate-Shen, C
AU  - Abate-Shen C
FAU - Shen, M M
AU  - Shen MM
LA  - eng
GR  - CA76501/CA/NCI NIH HHS/United States
GR  - R01 HD034883/HD/NICHD NIH HHS/United States
GR  - P30 CA034196/CA/NCI NIH HHS/United States
GR  - DK52721/DK/NIDDK NIH HHS/United States
GR  - R01 NS036437/NS/NINDS NIH HHS/United States
GR  - T32 MH019957/MH/NIMH NIH HHS/United States
GR  - R01 DK051101/DK/NIDDK NIH HHS/United States
GR  - CA59831/CA/NCI NIH HHS/United States
GR  - R01 CA076501/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (Homeodomain Proteins)
RN  - 0 (NKX3-1 protein, human)
RN  - 0 (Nkx3-1 protein, mouse)
RN  - 0 (Proteins)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Bulbourethral Glands/metabolism
MH  - Cell Differentiation
MH  - Epithelium
MH  - Gene Expression
MH  - Gene Targeting
MH  - *Genes, Tumor Suppressor
MH  - Homeodomain Proteins/genetics/*physiology
MH  - Humans
MH  - Male
MH  - Mice
MH  - Morphogenesis
MH  - Prostate/embryology/metabolism/pathology
MH  - Prostatic Hyperplasia/*etiology/genetics/pathology
MH  - Prostatic Neoplasms/*etiology/genetics/pathology
MH  - Proteins/metabolism
MH  - Transcription Factors/genetics/*physiology
PMC - PMC316645
EDAT- 1999/04/24 00:00
MHDA- 1999/04/24 00:01
CRDT- 1999/04/24 00:00
PHST- 1999/04/24 00:00 [pubmed]
PHST- 1999/04/24 00:01 [medline]
PHST- 1999/04/24 00:00 [entrez]
AID - 10.1101/gad.13.8.966 [doi]
PST - ppublish
SO  - Genes Dev. 1999 Apr 15;13(8):966-77. doi: 10.1101/gad.13.8.966.