Nkx3.1 mutant mice recapitulate early stages of prostate carcinogenesis.
Nkx3.1 mutant mice recapitulate early stages of prostate carcinogenesis.
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发表时间：
2002-06
期刊：
影响因子：
11.2
通讯作者：
Minjung Kim;R. Bhatia-Gaur;Whitney A. Banach-Petrosky;Nishita Desai;Yuzhuo Wang;S. Hayward;G. Cunha-G.
中科院分区：
文献类型：
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作者：
Minjung Kim;R. Bhatia-Gaur;Whitney A. Banach-Petrosky;Nishita Desai;Yuzhuo Wang;S. Hayward;G. Cunha-G.
最近对人类癌症和突变小鼠模型的研究表明，Nkx3.1同源框基因在前列腺癌的发生中起关键作用。与这种作用相一致，我们在这里表明，Nkx3.1在细胞培养中显示出生长抑制活性，并且老年Nkx3.1突变小鼠表现出类似于前列腺癌的组织病理学缺陷，PIN被认为是人类前列腺癌的先兆。利用组织重组方法，我们发现Nkx3.1突变体的PIN样病变在连续移植到裸鼠体内后可以经历逐渐严重的组织病理学变化。我们的发现表明，Nkx3.1功能丧失是前列腺癌发生的关键事件，Nkx3.1突变小鼠准确地模拟了前列腺癌发生的早期阶段。更广泛地说，我们的组织重组试验为检验PIN与前列腺癌的关系提供了一个经验性测试。
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.