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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Early onset of neoplasia in the prostate and skin of mice with tissue-specific deletion of Pten
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Early onset of neoplasia in the prostate and skin of mice with tissue-specific deletion of Pten

机译：Pten的组织特异性缺失在小鼠前列腺和皮肤中出现肿瘤的早期发作

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PTEN is a tumor suppressor gene mutated in various advanced human neoplasias, including glioblastomas and prostate, breast, endometrial, and kidney cancers. This tumor suppressor is a lipid phosphatase that negatively regulates cell survival and proliferation mediated by phosphatidylinositol 3-kinase protein kinase B signaling. Using the Cre-loxP system, we selectively inactivated Pten in murine tissues in which the MMTV-LTR promoter is active, resulting in hyperproliferation and neoplastic changes in Pten-null skin and prostate. These phenotypes had early onset and were completely penetrant. Abnormalities in Pten mutant skin consisted of mild epidermal hyperplasia, whereas prostates from these mice exhibited high-grade prostatic intraepitheliai neoplasia (HGPIN) that frequently progressed to focally invasive cancer. These data demonstrate that Pten is an important physiological regulator of growth in the skin and prostate. Further, the early onset of HGPIN in Pten mutant males is unique to this animal model and implicates PTEN mutations in the initiation of prostate cancer. Consistent with high PTEN mutation rates in human prostate tumors, these data indicate that PTEN is a critical tumor suppressor in this organ.
机译：PTEN是在各种晚期人类肿瘤中突变的肿瘤抑制基因，包括胶质母细胞瘤和前列腺癌，乳腺癌，子宫内膜癌和肾癌。该肿瘤抑制物是一种脂质磷酸酶，它负调节由磷脂酰肌醇3-激酶蛋白激酶B信号传导介导的细胞存活和增殖。使用Cre-loxP系统，我们选择性地灭活了MMTV-LTR启动子活跃的鼠组织中的Pten，导致Pten无效的皮肤和前列腺中过度增殖和肿瘤性改变。这些表型发病较早，完全渗透。 Pten突变体皮肤的异常包括轻度的表皮增生，而这些小鼠的前列腺表现出高级别的前列腺上皮内瘤样增生（HGPIN），经常发展为局部浸润性癌。这些数据表明，Pten是皮肤和前列腺生长的重要生理调节剂。此外，HGTEN在Pten突变雄性动物中的早期发作对该动物模型而言是独特的，并且在前列腺癌的发生中牵涉到PTEN突变。这些数据与人前列腺肿瘤中的高PTEN突变率一致，这些数据表明PTEN是该器官中的关键肿瘤抑制因子。

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