Nkx3.1; Pten mutant mice develop invasive prostate adenocarcinoma and lymph node metastases

Cory Abate-Shen, Whitney A. Banach-Petrosky, Xiaohui Sun, Kyriakos D. Economides, Nishita Desai, Jeffrey Gregg, Alexander D Borowsky, Robert Cardiff, Michael M. Shen

Research output: Contribution to journalArticle

185 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3886-3890
Number of pages5
JournalCancer Research
Volume63
Issue number14
StatePublished - Jul 15 2003

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Abate-Shen, C., Banach-Petrosky, W. A., Sun, X., Economides, K. D., Desai, N., Gregg, J., Borowsky, A. D., Cardiff, R., & Shen, M. M. (2003). Nkx3.1; Pten mutant mice develop invasive prostate adenocarcinoma and lymph node metastases. Cancer Research, 63(14), 3886-3890.