Physiological and pathological role of inositol phospholipids

在本研究中，我们分析了PTEN主要在细支气管肺泡上皮细胞、NKT细胞和尿路上皮细胞中的功能如下：1细支气管肺泡上皮细胞特异的Pten突变小鼠90%出生后不久就死于缺氧，存活的小鼠发生自发性肺腺癌。肺组织学检查显示细支气管肺泡上皮细胞和肌成纤维细胞前体细胞增生，表面活性蛋白的产生受损。细支气管肺泡干细胞(BASCs)的数量也增加了，BASCs可能是肺腺癌的始发者。这些结果表明，Pten对于正常的肺形态发生和预防肺癌的发生都是必不可少的，这可能是因为这种肿瘤抑制因子是BASC稳态所必需的。2 NKT细胞中的Pten突变导致Va14iNKT细胞发育失败。此外，Pten缺陷的Va14iNKT细胞在…反应中表现出增殖和细胞因子分泌减少更多的是在体外对αGalCer的刺激。在体内，在缺乏Pten的情况下，Va14iNKT细胞介导的对黑色素瘤细胞向肺转移的保护作用受到损害。因此，Pten/PI3K通路对于Va14iNKT细胞的动态平衡和抗肿瘤监视功能是不可或缺的。3所有小鼠的尿路上皮细胞特异性Pten零突变均表现为尿路上皮增生。随着时间的推移，10%的突变小鼠自发发展为带蒂乳头状移行细胞癌(TCC)。在人类中，超过一半的原发性膀胱癌患者表现出PTEN蛋白在肿瘤细胞的胞浆或胞核中表达减少或缺失。此外，我们还报道了电信号通过磷脂酰肌醇-3-羟基激酶-伽马和PTEN控制皮肤创伤的愈合；当靶向由大鼠胰岛素启动子驱动时，PTEN是身体大小和葡萄糖代谢的关键决定因素；在中性粒细胞中，通过PI(3，4，5)P3磷酸酶控制细胞的极性和运动性是由SHIP而不是PTEN控制的。较少

In this study, we have analyzed the functions of PTEN mainly in bronchioalveolar epithelial cells, NKT cells, and urothelial epithelial cells as follows;1 Ninety percent of bronchioalveolar epithelium-specific Pten mutant mice died of hypoxia soon after birth, and surviving mice developed spontaneous lung adenocarcinomas. Histological examinations of the lungs revealed hyperplasia of bronchioalveolar epithelial cells and myofibroblast precursors, and impaired production of surfactant proteins. Numbers of bronchioalveolar stem cells(BASCs), putative initiators of lung adenocarcinomas, were also increased. These results indicate that Pten is essential for both normal lung morphogenesis and the prevention of lung carcinogenesis, possibly because this tumor suppressor is required for BASC homeostasis.2 A failure in the development of Va14iNKT cells occurs by Pten mutation in NKT cells. In addition, Pten-deficient Va14iNKT cells show reduced proliferation and cytokine secretion in response … More to αGalCer stimulation in vitro. In vivo, Va14iNKT cell-mediated protection against the metastasis of melanoma cells to the lung was impaired in the absence of Pten. Thus, the Pten/PI3K pathway is indispensable for the homeostasis and antitumor surveillance function of Va14iNKT cells.3 All urothelium-specific null mutation of Pten in mice exhibited urothelial hyperplasia. With time, 10% of mutant mice spontaneously developed pedicellate papillary transitional cell carcinomas(TCC). In humans, more than half of primary bladder cancer patients exhibited decreased or absent expression of PTEN protein in either the cytoplasm or nucleus of tumor cells. Thus, PTEN deficiency may contribute to bladder cancer.4 Furthermore, we reported that electrical signals control skin wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN; PTEN is a critical determinant of body size and glucose metabolism when targeting is driven by the rat insulin promoter; and control of cell polarity and motility by PI(3,4,5) P3 phosphatase is governed by SHIP rather than PTEN in neutrophils. Less