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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >P21~(cip1) Restrains Pituitary Tumor Growth
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P21~(cip1) Restrains Pituitary Tumor Growth

机译：P21〜（cip1）抑制垂体肿瘤的生长

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摘要

As commonly encountered, pituitary adenomas are invariably benign. We therefore studied protective pituitary proliferative mechanisms. Pituitary tumor transforming gene (Pttg) deletion results in pituitary p21 induction and abrogates tumor development in Rb~(+/-)Pttg~(-/-) mice. p21 disruption restores attenuated Rb~(+/-)Pttg~(-/-) pituitary proliferation rates and enables high penetrance of pituitary, but not thyroid, tumor growth in triple mutant animals (88% of Rb~(+/-) and 72% of Rb~(+/-)Pttg~(-/-)p21~(-/-) vs. 30% of Rb~(+/-)Pttg~(-/-) mice developed pituitary tumors, P < 0.001). p21 deletion also accelerated S-phase entry and enhanced transformation rates in triple mutant MEFs. Intranuclear p21 accumulates in Pttg-null aneuploid GH-secreting cells, and GH_3 rat pituitary tumor cells overexpressing PTTG also exhibited increased levels of mRNA for both p21 (18-fold, P < 0.01) and ATM (9-fold, P < 0.01). PTTG is abundantly expressed in human pituitary tumors, and in 23 of 26 GH-producing pituitary adenomas with high PTTG levels, senescence was evidenced by increased p21 and SA-β-galactosidase. Thus, either deletion or overexpression of Pttg promotes pituitary cell aneuploidy and p53/p21 -dependent senescence, particularly in GH-secreting cells. Aneuploid pituitary cell p21 may constrain pituitary tumor growth, thus accounting for the very low incidence of pituitary carcinomas.
机译：如通常所见，垂体腺瘤总是良性的。因此，我们研究了保护性垂体增生机制。垂体肿瘤转化基因（Pttg）删除导致垂体p21诱导和废除Rb〜（+/-）Pttg〜（-/-）小鼠的肿瘤发展。 p21破坏可恢复减毒的Rb〜（+/-）Pttg〜（-/-）垂体增生速率，并能使三重突变动物的垂体（而非甲状腺）肿瘤生长具有较高的穿透性（Rb〜（+/-）和88％的Rb〜（+/-） 72％的Rb〜（+/-）Pttg〜（-/-）p21〜（-/-）小鼠中有30％的Rb〜（+/-）Pttg〜（-/-）小鼠患有垂体瘤，P < 0.001）。 p21缺失还加速了三重突变MEF中的S期进入并提高了转化率。核内p21会在无Pttg的非整倍体GH分泌细胞中积聚，并且过表达PTTG的GH_3大鼠垂体瘤细胞的p21（18倍，P <0.01）和ATM（9倍，P <0.01）的mRNA水平也均升高。 。 PTTG在人的垂体瘤中大量表达，在26种GH产生的GH垂体腺瘤中，PTTG高水平的23例中，p21和SA-β-半乳糖苷酶增加证明了衰老。因此，Pttg的缺失或过度表达促进垂体细胞非整倍性和p53 / p21依赖性衰老，特别是在分泌GH的细胞中。非整倍体垂体细胞p21可能会限制垂体肿瘤的生长，因此占垂体癌的发生率很低。

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