| Expression of metabolically targeted biomarkers in endometrial carcinoma. | |
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MedLine Citation:
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PMID: 19878980 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. |
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Authors:
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Heather Wahl; Sayeema Daudi; Malti Kshirsagar; Kent Griffith; Lijun Tan; Jennifer Rhode; J Rebecca Liu |
Publication Detail:
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Type: Journal Article Date: 2009-10-29 |
Journal Detail:
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Title: Gynecologic oncology Volume: 116 ISSN: 1095-6859 ISO Abbreviation: Gynecol. Oncol. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2009-12-07 Completed Date: 2009-12-11 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0365304 Medline TA: Gynecol Oncol Country: United States |
Other Details:
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Languages: eng Pagination: 21-7 Citation Subset: IM |
Affiliation:
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Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Combined Chemotherapy Protocols
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pharmacology* Apoptosis / drug effects Cell Growth Processes / drug effects Cell Line, Tumor Cisplatin / pharmacology Deoxyglucose / pharmacology Drug Delivery Systems Drug Synergism Endometrial Neoplasms / drug therapy*, metabolism*, pathology Female Glucose Transporter Type 1 / antagonists & inhibitors, biosynthesis Humans Protein Kinases / biosynthesis, metabolism Proto-Oncogene Proteins c-akt / antagonists & inhibitors, biosynthesis Signal Transduction / drug effects Sirolimus / pharmacology Tumor Markers, Biological / antagonists & inhibitors*, biosynthesis |
| Chemical | |
Reg. No./Substance:
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0/Glucose Transporter Type 1; 0/SLC2A1 protein, human; 0/Tumor Markers, Biological; 154-17-6/Deoxyglucose; 15663-27-1/Cisplatin; 53123-88-9/Sirolimus; EC 2.7.-/Protein Kinases; EC 2.7.1.-/mTOR protein; EC 2.7.11.1/Proto-Oncogene Proteins c-akt |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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