P-LAP/IRAP-induced cell proliferation and glucose uptake in endometrial carcinoma cells via insulin receptor signaling.
P-LAP/IRAP-induced cell proliferation and glucose uptake in endometrial carcinoma cells via insulin receptor signaling.
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DOI：
10.1186/1471-2407-7-15
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发表时间：
2007-01-19
期刊：
影响因子：
3.8
通讯作者：
Kikkawa F
中科院分区：
文献类型：
--
作者：
Shibata K;Kajiyama H;Ino K;Nawa A;Nomura S;Mizutani S;Kikkawa F
高血糖或高胰岛素血症会导致子宫内膜癌生存率较差。结果表明，P-LAP/IRAP 响应胰岛素刺激而易位至质膜。最近，我们证明 P-LAP/IRAP 与子宫内膜腺癌患者的不良预后相关。本研究的目的是检查 P-LAP/IRAP 增强子宫内膜癌的恶性潜力是否是由于 P-LAP/IRAP 介导的胰岛素信号激活增加了葡萄糖摄取。我们将 P-LAP/IRAP cDNA 转染到 A-MEC 细胞（子宫内膜腺癌细胞系）中，A-MEC-LAP 细胞表达了非常高水平的 GLUT4 蛋白。 A-MEC-LAP细胞对胰岛素反应的3H-2-脱氧葡萄糖摄取显着高于A-MEC-pc细胞。与 A-MEC-pc 细胞相比，A-MEC-LAP 细胞表现出显着的生长刺激作用。与 A-MEC-pc 细胞相比，A-MEC-LAP 细胞表达显着高水平的 p85PI3K 蛋白，并且在胰岛素刺激下表现出更高程度的 AKT 磷酸化。总之，P-LAP/IRAP 参与了胰岛素介导的子宫内膜癌恶性潜能的增加。 P-LAP/IRAP被认为是子宫内膜癌分子靶向治疗的潜在新靶点。
Hyperglycemia or hyperinsulinemia contributes to poorer endometrial cancer survival. It was shown that P-LAP/IRAP translocates to the plasma membrane in response to insulin stimulation. Recently, we demonstrated that P-LAP/IRAP is associated with a poor prognosis in endometrial adenocarcinoma patients. The aim of this study was to examine whether the malignant potential of endometrial cancer enhanced by P-LAP/IRAP is due to increased glucose uptake via the P-LAP/IRAP-mediated activation of insulin signaling. We transfected P-LAP/IRAP cDNA into A-MEC cells (endometrial adenocarcinoma cell line), and A-MEC-LAP cells expressed a remarkably high level of GLUT4 proteins. 3H-2-deoxyglucose uptake which responds to insulin in A-MEC-LAP cells was significantly higher than that of A-MEC-pc cells. A-MEC-LAP cells exhibited a significant growth-stimulatory effect compared to A-MEC-pc cells. A-MEC-LAP cells expressed a remarkably high level of p85PI3K protein compared to A-MEC-pc cells, and showed a higher degree of AKT phosphorylation by insulin stimulation. In summary, P-LAP/IRAP was involved in the increasing malignant potential of endometrial cancer mediated by insulin. P-LAP/IRAP was suggested to be a potential new target of molecular-targeted therapy for endometrial cancer.
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