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Publication : Nkx3.1 mutant mice recapitulate early stages of prostate carcinogenesis.

First Author  Kim MJ Year  2002
Journal  Cancer Res Volume  62
Issue  11 Pages  2999-3004
PubMed ID  12036903 Mgi Jnum  J:77034
Mgi Id  MGI:2180925 Citation  Kim MJ, et al. (2002) Nkx3.1 mutant mice recapitulate early stages of prostate carcinogenesis. Cancer Res 62(11):2999-3004
abstractText  Recent studies of human cancers and mutant mouse models have implicated the Nkx3.1 homeobox gene as having a key role in prostate carcinogenesis. Consistent with such a role, here we show that Nkx3.1 displays growth-suppressing activities in cell culture, and that aged Nkx3.1 mutant mice display histopathological defects resembling prostatic intraepithelial neoplasia (PIN), the presumed precursor of human prostate cancer. Using a tissue recombination approach, we found that PIN-like lesions from Nkx3.1 mutants can undergo progressively severe histopathological alterations after serial transplantation in nude mice. Our findings indicate that Nkx3.1 loss-of-function is a critical event in prostate cancer initiation, and that Nkx3.1 mutant mice accurately model early stages of prostate carcinogenesis. More generally, our tissue recombination assay provides an empirical test to examine the relationship of PIN to prostate carcinoma.
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