Nkx3.1; Pten mutant mice develop invasive prostate adenocarcinoma and lymph node metastases
- PMID: 12873978
Nkx3.1; Pten mutant mice develop invasive prostate adenocarcinoma and lymph node metastases
Abstract
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.
Similar articles
-
Vitamin D inhibits the formation of prostatic intraepithelial neoplasia in Nkx3.1;Pten mutant mice.Clin Cancer Res. 2006 Oct 1;12(19):5895-901. doi: 10.1158/1078-0432.CCR-06-1039. Clin Cancer Res. 2006. PMID: 17020998
-
Cooperativity of Nkx3.1 and Pten loss of function in a mouse model of prostate carcinogenesis.Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2884-9. doi: 10.1073/pnas.042688999. Epub 2002 Feb 19. Proc Natl Acad Sci U S A. 2002. PMID: 11854455 Free PMC article.
-
Nkx3.1 mutant mice recapitulate early stages of prostate carcinogenesis.Cancer Res. 2002 Jun 1;62(11):2999-3004. Cancer Res. 2002. PMID: 12036903
-
Mechanisms of prostate tumorigenesis: roles for transcription factors Nkx3.1 and Egr1.Ann N Y Acad Sci. 2005 Nov;1059:33-40. doi: 10.1196/annals.1339.018. Ann N Y Acad Sci. 2005. PMID: 16382041 Review.
-
Molecular mechanisms of prostate cancer.Eur Urol. 2004 Jun;45(6):683-91. doi: 10.1016/j.eururo.2004.01.012. Eur Urol. 2004. PMID: 15149739 Review.
Cited by
-
Additive Effect of Zfhx3/Atbf1 and Pten Deletion on Mouse Prostatic Tumorigenesis.J Genet Genomics. 2015 Jul 20;42(7):373-82. doi: 10.1016/j.jgg.2015.06.004. Epub 2015 Jun 25. J Genet Genomics. 2015. PMID: 26233892 Free PMC article.
-
Germ-line sequence variants of PTEN do not have an important role in hereditary and non-hereditary prostate cancer susceptibility.J Hum Genet. 2011 Jul;56(7):496-502. doi: 10.1038/jhg.2011.48. Epub 2011 Jun 2. J Hum Genet. 2011. PMID: 21633361 Free PMC article.
-
Genome-wide promoter analysis of the SOX4 transcriptional network in prostate cancer cells.Cancer Res. 2009 Jan 15;69(2):709-17. doi: 10.1158/0008-5472.CAN-08-3415. Cancer Res. 2009. PMID: 19147588 Free PMC article.
-
The role of peroxisome proliferator-activated receptor gamma in prostate cancer.Asian J Androl. 2018 May-Jun;20(3):238-243. doi: 10.4103/aja.aja_15_17. Asian J Androl. 2018. PMID: 28597850 Free PMC article. Review.
-
Deletion of 8p is an independent prognostic parameter in prostate cancer.Onco_target. 2017 Jan 3;8(1):379-392. doi: 10.18632/onco_target.13425. Onco_target. 2017. PMID: 27880722 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Other Literature Sources
Medical
Molecular Biology Databases
Research Materials