Wei Zhang

Pathology - Research, Pathology/Lab Medicine - Resch

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Mitogenic and anti-apoptotic effects of insulin in endometrial cancer are phosphatidylinositol 3-kinase/Akt dependent

Yingmei Wang; Shaofang Hua; Wenyan Tian; Lizhi Zhang; Jing Zhao; Huiying Zhang; Wei Zhang; Fengxia Xue (Profiled Author: Wei Zhang)

Gynecologic Oncology. 2012;125(3):734-741.

Objective: To determine serum insulin levels, expression and phosphorylation of InsR, IRS-1 and Akt in endometrial cancer (EC) tissues, and to explore the correlation between them. To investigate if insulin-induced mitogenic and anti-apoptotic effects are PI3K-dependent in EC cells. Methods: Serum insulin levels were measured by radioimmunoassay. We performed RT-PCR and western blotting to evaluate the expression and activation of key proteins of PI3K/Akt pathway in 63 EC tissues. The proliferation and apoptosis rates were determined with MTT, BrdU and annexin V/PI assays. Results: Serum insulin levels and InsR, IRS-1 and Akt expression and phosphorylation were significantly elevated in patients with EC compared to those without EC. Additionally, levels of p-InsR, p-IRS-1, and p-Akt were significantly higher in patients with high-grade, advanced stage, deep myometrial invasion, and lymph-node metastasis. The expression and activation of InsR, IRS-1, and p-Akt were positively related with the levels of serum insulin. The insulin-induced mitogenic and anti-apoptotic effects in EC cells were blocked when cells were pre-incubated with LY294002. Ishikawa 3-H-12 cells showed increased p-Akt levels after treatment with insulin at 10 ^{- 8} M for 15 min. The insulin-induced Akt activation was inhibited by LY294002 in a dose-dependent manner. Conclusion: Insulin played an essential role in EC tumorigenesis. Activation of InsR, IRS-1, and Akt was associated with features of aggressive EC. Insulin was a mitogenic and anti-apoptotic agent for EC cells, and these effects were dependent on PI3K/Akt pathway. Decreasing insulin level and blocking the InsR-IRS-PI3K-Akt pathway could be viable preventive and therapeutic strategies for EC. © 2012 Elsevier Inc. All rights reserved.

PMID: 22426488    

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