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Abate-Shen, C. et al.

Abate-Shen, Banach-Petrosky, Sun, Economides, Desai, Gregg, Borowsky, Cardiff, Shen,

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.[1]

References

Nkx3.1; Pten mutant mice develop invasive prostate adenocarcinoma and lymph node metastases. Abate-Shen, C., Banach-Petrosky, W.A., Sun, X., Economides, K.D., Desai, N., Gregg, J.P., Borowsky, A.D., Cardiff, R.D., Shen, M.M. Cancer Res. (2003) [Pubmed]

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