GLUT1 messenger RNA and protein induction relates to the malignant transformation of cervical cancer.
We studied whether induction of glucose transporters (GLUTs) 1 to 4 correlates with human papillomavirus (HPV)-dependent malignant transformation of cervical epithelium. Tissue samples of cervical intraepithelial neoplasia (CIN; grades 1 to 3), invasive carcinomas, and lymph node metastasis were examined. HPV typing was performed. Tissue sections were immunostained with GLUT1 to GLUT4 antibodies. Messenger RNA (mRNA) in situ hybridization confirmed GLUT1 protein expression. Weak expression of GLUT1 was found in nondysplastic HPV-positive and HPV-negative epithelium; significant expression was observed in preneoplastic lesions, correlating with the degree of dysplasia. In CIN 3 high-risk HPV lesions, cervical cancer, and metastasis, GLUT1 was expressed at highest levels with a strong correlation of GLUT1 mRNA and protein expression. Immunostains for GLUT2 to GLUT4 were negative. Cervical tumor cells respond to enhanced glucose utilization by up-regulation of GLUT1. The strong induction of GLUT1 mRNA and protein in HPV-positive CIN 3 lesions suggests GLUT1 overexpression as an early event in cervical neoplasia. GLUT1 is potentially relevant as a diagnostic tool and glucose metabolism as a therapeutic target in cervical cancer.
Rudlowski
Christian
C
Dept of Gynecology and Obstetrics, University Hospital Heidelberg, Vossstr 7-9, D-69115 Heidelberg, Germany.
Becker
Albert J
AJ
Schroder
Willibald
W
Rath
Werner
W
Büttner
Reinhard
R
Moser
Markus
M
D002471:Cell Transformation, Neoplastic; D005260:Female; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1; D006801:Humans; D007150:Immunohistochemistry; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000235:genetics*; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis*; D002583:Uterine Cervical Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495677:SLC2A1 protein, human; D005947:Glucose