Glucose-transporter-type-I-gene amplification correlates with sialyl-Lewis-X synthesis and proliferation in lung cancer.
Increased glucose transport is a common characteristic of most tumors. To examine the role of elevated glucose uptake in lung cancer, we performed PCR amplification of 2 facilitative glucose transporter genes (GLUT1 and GLUT3) and immunohistochemical staining for GLUT1, proliferating cell nuclear antigen (PCNA), and sialyl Lewis x (sLe(x)) on tumor specimens from 327 patients with lung cancer who underwent surgical resection from 1980 to 1993. To evaluate the relationship between GLUT, alpha-2,3-sialyltransferase (ST), and alpha-1,3-fucosyltransferase (Fuc-T) genes, PCR amplification of the ST3N and Fuc-TVII also was performed. Amplification of GLUT1 was significantly greater than that of GLUT3. GLUT1 and GLUT3 amplification correlated with PCNA staining (p < 0.01). In addition, GLUT1 amplification correlated with the grading of sLe(x) staining as well as with the grading of GLUT1 staining (p < .03, p < 0.01). GLUT1 was co-amplified with ST3N and Fuc-TVII genes, which are involved in the synthesis of sLe(x) (p < 0.01). The survival of patients whose tumors showed GLUT1 amplification was significantly shorter than that of patients whose tumors did not (p < 0.01). In a multivariate analysis of survival, GLUT1 remained a statistically significant prognostic factor. Our results suggest that GLUT1 amplification may participate in sLe(x) synthesis as well as in proliferation, and may be of prognostic value in lung cancer.
Ogawa
J
J
First Department of Surgery, School of Medicine, Tokai University, Kanagawa, Japan.
Inoue
H
H
Koide
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002455:Cell Division; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism; D005784:Gene Amplification; D006801:Humans; D016256:Lewis X Antigen / Q000096:biosynthesis*; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000378:metabolism; D015999:Multivariate Analysis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis
D016256:Lewis X Antigen; D009004:Monosaccharide Transport Proteins; D018809:Proliferating Cell Nuclear Antigen; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase; D012799:Sialyltransferases