Nkx3.1; Pten mutant mice develop invasive prostate adenocarcinoma and lymph node metastases.
Recent studies have shown that several loss-of-function mouse models of prostate carcinogenesis can develop a spectrum of precancerous lesions that resemble human prostatic intraepithelial neoplasia (PIN). Here, we have investigated the malignant potential of the high-grade PIN lesions that form in Nkx3.1(+/-); Pten(+/-) compound mutant mice and demonstrate their neoplastic progression in a serial transplantation/tissue recombination assay. Furthermore, we find that a majority of Nkx3.1(+/-); Pten(+/-) mice greater than 1 year of age develop invasive adenocarcinoma, which is frequently accompanied by metastases to lymph nodes. Finally, we observe androgen independence of high-grade PIN lesions after androgen ablation of Nkx3.1(+/-); Pten(+/-) mice. We conclude that Nkx3.1(+/-); Pten(+/-) mice recapitulate key features of advanced prostate cancer and represent a useful model for investigating associated molecular mechanisms and for evaluating therapeutic approaches.
Abate-Shen
Cory
C
Center for Advanced Biotechnology and Medicine, University of Medicine and Dentistry, New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA. abate@cabm.rutgers.edu
Banach-Petrosky
Whitney A
WA
Sun
Xiaohui
X
Economides
Kyriakos D
KD
Desai
Nishita
N
Gregg
Jeffery P
JP
Borowsky
Alexander D
AD
Cardiff
Robert D
RD
Shen
Michael M
MM
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D000818:Animals; D004195:Disease Models, Animal; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009154:Mutation; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009919:Orchiectomy; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D051381:Rats; D013739:Testosterone / Q000097:blood; D014157:Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D018398:Homeodomain Proteins; C491178:NKX3-1 protein, human; C102837:Nkx3-1 protein, mouse; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D013739:Testosterone; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human