| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 3945049 | Gynecologic Oncology | 2012 | 8 Pages |
ObjectiveTo 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.MethodsSerum 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.ResultsSerum 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.ConclusionInsulin 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.
► Insulin levels were significantly elevated in patients with endometrial cancer. ► Activation of InsR, IRS-1, and Akt was higher in patients with advanced stage and positively correlated with insulin levels. ► The mitogenic and anti-apoptosis effects of insulin on EC cells are dependent on InsR and PI3K/Akt pathway.
