Document Detail


Expression of metabolically targeted biomarkers in endometrial carcinoma.
MedLine Citation:
PMID:  19878980     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Heather Wahl; Sayeema Daudi; Malti Kshirsagar; Kent Griffith; Lijun Tan; Jennifer Rhode; J Rebecca Liu
Publication Detail:
Type:  Journal Article     Date:  2009-10-29
Journal Detail:
Title:  Gynecologic oncology     Volume:  116     ISSN:  1095-6859     ISO Abbreviation:  Gynecol. Oncol.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2009-12-07     Completed Date:  2009-12-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0365304     Medline TA:  Gynecol Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  21-7     Citation Subset:  IM    
Affiliation:
Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Combined Chemotherapy Protocols / 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:
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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