Enhanced expression of glucose transporter GLUT3 in tumorigenic HeLa cell hybrids associated with tumor suppressor dysfunction.
Previous studies on human cell hybrids between HeLa and normal human fibroblasts have indicated that the tumorigenicy may be controlled by a putative tumor suppressor gene on chromosome 11. We previously demonstrated a twofold increase in glucose uptake with a reduced Km by tumorigenic HeLa cell hybrids which expressed a highly glycosylated GLUT1. In this study, we reported that a tumorigenic cell hybrid, CGL4, also expressed a glucose transporter isoform, GLUT3, that was undetectable in nontumorigenic CGL1 cells. The expression of GLUT3 together with GLUT1 of 70 kDa was also evident in three gamma-ray-induced tumorigenic clones isolated from CGL1 cells, while control nontumorigenic irradiated cells expressed 50 kDa GLUT1 alone. In accordance with this, GLUT3 mRNA was specifically expressed in tumorigenic cell hybrids. To examine the role of GLUT3, clones which stably overexpress GLUT3 were developed from both CGL1 and CGL4 cells. In these transfectants, the affinity for 2-deoxyglucose markedly increased, in parallel with the amount of expressed GLUT3 irrespective of its N-glycosylation state. These results suggest that the enhanced GLUT3 expression in HeLa cell hybrids associated with the tumorigenic phenotypes may account for the increased affinity for 2-deoxyglucose. Possible roles of the putative tumor suppressor in control of gene expression and glucose uptake is discussed.
Suzuki
T
T
Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Tokyo, Japan.
Iwazaki
A
A
Katagiri
H
H
Oka
Y
Y
Redpath
J L
JL
Stanbridge
E J
EJ
Kitagawa
T
T
D001692:Biological Transport; D018076:DNA, Complementary; D016147:Genes, Tumor Suppressor; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D006367:HeLa Cells; D006801:Humans; D006822:Hybrid Cells; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger / Q000235:genetics; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection
D018076:DNA, Complementary; 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; D005947:Glucose