Expression of metabolically targeted biomarkers in endometrial carcinoma
| Autor: | J. Rebecca Liu, Sayeema Daudi, Lijun Tan, Malti Kshirsagar, Jennifer M. Rhode, Heather Wahl, Kent A. Griffith |
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| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
Glucose uptake Apoptosis Cell Growth Processes Deoxyglucose Article Drug Delivery Systems Internal medicine Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols medicine Carcinoma Biomarkers Tumor Cytotoxic T cell Humans PI3K/AKT/mTOR pathway Sirolimus Glucose Transporter Type 1 biology business.industry TOR Serine-Threonine Kinases Glucose transporter Obstetrics and Gynecology Drug Synergism medicine.disease Endometrial Neoplasms Endocrinology Oncology biology.protein Cancer research GLUT1 Female Cisplatin business Protein Kinases Proto-Oncogene Proteins c-akt medicine.drug Signal Transduction |
| Zdroj: | Gynecologic oncology. 116(1) |
| ISSN: | 1095-6859 |
| Popis: | The differential metabolic phenotype observed between malignant and non-transformed cells may constitute a biochemical basis for therapeutic intervention. Increased glucose uptake is one of the major metabolic changes found in malignant tumors, a process that is mediated by glucose transporters such as Glut1. Cellular growth can be regulated by mTOR in response to the nutrient milieu. In this study, we sought to determine if endometrial carcinoma cells express Glut1 and mTOR, and if inhibition of these factors is cytotoxic to endometrial carcinoma cells in vitro.Expression of Glut1, pAkt, and pmTOR was assessed in tissue microarrays constructed from 42 type I and 34 type II endometrial tumors by immunohistochemistry, and in a panel of endometrial carcinoma cell lines. Representative endometrial carcinoma cells with wild type or mutant endogenous PTEN were treated with the glucose analog 2-deoxyglucose (2-DG) and rapamycin, an mTOR inhibitor or cisplatin. Inhibition of cell growth and mechanism of cell death was determined.Glut1, pAkt, and pmTOR were expressed strongly in both types I and II endometrial carcinoma. 2-DG and rapamycin induced apoptotic cell death in type I endometrial carcinoma cells, and profound growth inhibition and cytostasis in type II endometrial carcinoma cells.Glut1, pAkt, and pmTOR are overexpressed in endometrial carcinomas. Distinct alterations in the phosphatidylinositol 3'-kinase (PI3K) pathway upstream of mTOR, such as pAkt, may identify endometrial carcinoma patients who may benefit from adjuvant treatment with mTOR inhibitors and/or glucose analogs. |
| Databáze: | OpenAIRE |
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