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P-LAP/IRAP通过胰岛素受体信号通路诱导子宫内膜癌细胞增殖和葡萄糖摄取。

P-LAP/IRAP-induced cell proliferation and glucose uptake in endometrial carcinoma cells via insulin receptor signaling.

作者信息

Shibata Kiyosumi, Kajiyama Hiroaki, Ino Kazuhiko, Nawa Akihiro, Nomura Seiji, Mizutani Shigehiko, Kikkawa Fumitaka

机构信息

Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

出版信息

BMC Cancer. 2007 Jan 19;7:15. doi: 10.1186/1471-2407-7-15.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

高血糖或高胰岛素血症会导致子宫内膜癌患者的生存率降低。研究表明,P-LAP/IRAP会在胰岛素刺激下转位至质膜。最近,我们证实P-LAP/IRAP与子宫内膜腺癌患者的不良预后相关。本研究的目的是探讨P-LAP/IRAP增强子宫内膜癌恶性潜能是否是由于通过P-LAP/IRAP介导的胰岛素信号激活增加了葡萄糖摄取。

方法

我们将P-LAP/IRAP cDNA转染至A-MEC细胞(子宫内膜腺癌细胞系),A-MEC-LAP细胞表达了高水平的GLUT4蛋白。

结果

A-MEC-LAP细胞中对胰岛素有反应的3H-2-脱氧葡萄糖摄取显著高于A-MEC-pc细胞。与A-MEC-pc细胞相比,A-MEC-LAP细胞表现出显著的生长刺激作用。与A-MEC-pc细胞相比,A-MEC-LAP细胞表达了高水平的p85PI3K蛋白,并且在胰岛素刺激下显示出更高程度的AKT磷酸化。

结论

总之,P-LAP/IRAP参与了胰岛素介导的子宫内膜癌恶性潜能增加。P-LAP/IRAP被认为是子宫内膜癌分子靶向治疗的潜在新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dded/1781462/10d6b7cd2e25/1471-2407-7-15-1.jpg

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