GLUT1 mRNA and protein expression in ovarian borderline tumors and cancer.
OBJECTIVE
Increased glucose uptake and utilization is a major feature of malignant tumors. Recent studies suggest that the key mechanism of enhanced glucose metabolism in carcinoma cells involves the overexpression of transmembrane glucose transporter proteins (GLUTs). The aim of the present study was to analyze the expression of different GLUT isoforms (GLUT1-4) and to investigate whether alterations in their expression pattern accompany the malignant transformation and progression of ovarian cancer.


METHODS
Tumor tissue of 94 patients suffering from primary ovarian cancer (n = 78) or borderline tumors (n = 16) and tissue from 16 patients with benign ovarian changes were examined in this study. Immunohistochemistry was performed using polyclonal GLUT1-4 antibodies. GLUT1 protein expression was quantified by Western blot analysis. GLUT1 mRNA expression was analyzed by mRNA in situ hybridization.


RESULTS
All of the invasive carcinomas were positive for GLUT1. In contrast, GLUT1 expression was moderate in borderline tumors and weak to negative in all benign ovarian neoplasms. High GLUT1 mRNA levels were observed only in ovarian cancer. The intensity of GLUT1 expression in malignant ovarian neoplasms was associated neither with tumor characteristics nor with patient survival. Only GLUT3 revealed weak but homogeneous expression in human ovarian cancer as well as in benign ovarian tumors. GLUT2 and GLUT4 showed no expression in ovarian tissue.


CONCLUSIONS
GLUT1 mRNA and protein were found to be expressed specifically in primary ovarian cancer. The close relationship between GLUT1 mRNA and protein expression points towards the potential relevance of GLUT1 as a diagnostic tool and therapeutic target in ovarian cancer.
Department of Gynecology and Obstetrics, University Hospital Heidelberg, Heidelberg, Germany. Rudlowski@t-online.de
Christian
C
Rudlowski
Markus
M
Moser
Albert J
AJ
Becker
Werner
W
Rath
Reinhard
R
Buttner
Willibald
W
Schroder
Annette
A
Schurmann
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D005260:Female; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D015996:Survival Rate
D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C495677:SLC2A1 protein, human; C495687:SLC2A3 protein, human