Skip to main content
PMC home page
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 2001 Aug;92(8):874–879. doi: 10.1111/j.1349-7006.2001.tb01175.x

SGLT Gene Expression in Primary Lung Cancers and Their Metastatic Lesions

Nobuhisa Ishikawa 1, Tetsuya Oguri 1,✉, Takeshi Isobe 1, Kazunori Fujitaka 1, Nobuoki Kohno 1
PMCID: PMC5926833  PMID: 11509120

Abstract

Cancer cells show increased glucose uptake and utilization in comparison with their normal counterparts. Glucose transporters play an important role in glucose uptake. We previously reported the differential gene expression of the GLUT family in primary and metastatic lesions of lung cancer. To investigate the role of Na+/glucose cotransporter (SGLT) genes in cancers, we examined the levels of expression of SGLT1 and SGLT2 genes in primary lung cancers and their metastatic lesions. Ninety‐six autopsy samples (35 primary lung cancers, 35 corresponding normal lung tissues, 10 metastatic liver lesions, and 16 metastatic lymph nodes) from 35 patients were analyzed for SGLT1 and SGLT2 expression by reverse transcription (RT)‐polymerase chain reaction (PCR). There were no significant differences in the level of expression of either gene between the primary lung cancers and normal lung tissues. The level of SGLT1 expression in the metastatic lesions and primary lung cancers did not differ significantly. The level of SGLT2 expression was, however, significantly higher in the metastatic lesions of both the liver and lymph node than in the primary lung cancers. These results suggest that SGLT2 plays a role in glucose uptake in the metastatic lesions of lung cancer.

Keywords: SGLT1, SGLT2, Lung cancer

Full Text

The Full Text of this article is available as a PDF (136.3 KB).

References

  • 1.Isselbacher , K. J.Sugar and amino acid transport by cells in culture‐differences between normal and malignant cells . N. Engl. J. Med. , 286 , 929 – 933 ( 1972. ). [DOI] [PubMed] [Google Scholar]
  • 2.Holm , E. , Hagmuller , E. , Staedt , U. , Schlickeiser , G. , Gunther , H. J. , Leweling , H. , Tokus , M. and Kollmar , H. B.Substrate balances across colonic carcinomas in humans . Cancer Res. , 55 , 1317 – 1378 ( 1995. ). [PubMed] [Google Scholar]
  • 3.Blair , S. L. , Heerdt , P. , Sachar , S. , Abolhoda , A. , Hochwald , S. , Cheng , H. and Burt , M.Glutathione metabolism in patients with non‐small cell lung cancers . Cancer Res. , 57 , 152 – 155 ( 1997. ). [PubMed] [Google Scholar]
  • 4.Pessin , J. E. and Bell , G. I.Mammalian facilitative glucose transporter family: structure and molecular regulation . Annu. Rev. Physiol , 54 , 911 – 930 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 5.Bell , G. L , Burant , C. F. , Takeda , J. and Gould , G. W.Structure and function of mammalian facilitative sugar transporters . J. Biol. Chem. , 268 , 19161 – 19164 ( 1993. ). [PubMed] [Google Scholar]
  • 6.Hediger , H. A. , Truk , E. and Wright , E. M.Homology of the human intestinal Na+/glucose and Escherichia coli Na+/proline cotransporters . Proc. Natl. Acad. Sci. USA , 86 , 5748 – 5752 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Wells , R. G. , Pajor , A. M. , Kanai , Y. , Turk , E. , Wright , E. M. and Hediger , M. A.Cloning of a human kidney cDNA with similarity to the sodium‐glucose cotransporter . Am. J. Physiol. , 263 , F459 – F465 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 8.Lee , W. S. , Kanai , Y. , Wells , R. G. and Hediger , M. A.The high affinity Na+/glucose cotransporter. Re‐evaluation of function and distribution of expression . J. Biol. Chem. , 269 , 12032 – 12039 ( 1994. ). [PubMed] [Google Scholar]
  • 9.Kanai , Y. , Lee , W. S. , You , G. , Brown , D. and Hediger , M. A.The human kidney low affinity Na+/glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D‐glucose . J. Clin. Invest. , 93 , 397 – 404 ( 1994. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Younes , M. , Lechago , L. V. , Smoano , J. R. , Mosharaf , M. and Lechago , J.Wide expression of the erythrocyte glucose transporter Glutl in human cancers . Cancer Res. , 56 , 1164 – 1167 ( 1996. ). [PubMed] [Google Scholar]
  • 11.Younes , M. , Lechago , L. V. , Smoano , J. R. , Mosharaf , M. and Lechago , J.Immunohistochemical detection of Glut3 in human tumors and normal tissues . Anticancer Res. , 17 , 2747 – 2750 ( 1997. ). [PubMed] [Google Scholar]
  • 12.Zamora‐Leon , S. P. , Golde , D. W. , Concha , I. I , Rivas , C. L , Delgado‐Lopez , F. , Baselga , J. , Nualart , F. and Vera , J. C.Expression of the fructose transporter GLUTS in human breast cancer . Proc. Natl. Acad. Sci. USA , 93 , 1847 – 1852 ( 1996. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Kurata , T. , Oguri , T. , Isobe , T. , Ishioka , S. and Yamakido , M.Differential expression of facilitative glucose transporter (GLUT) genes in primary lung cancers and their liver metastases . Jpn. J. Cancer Res. , 90 , 1238 – 1243 ( 1999. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Oguri , T. , Fujiwara , Y. , Isobe , T. , Katoh , O. , Watanabe , H. and Yamakido , M.Expression of γ‐glutamylcysteine synthetase (γ‐GCS) and multidrug resistance‐associated protein (MRP), but not human canalicular multispecific organic anion transporter (cMOAT), genes correlates with exposure of human lung cancers to platinum drugs . Br. J. Cancer , 77 , 1089 – 1096 ( 1998. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Matosin‐Matekalo , M. , Mesonero , J. E. , Delezay , O. , Poiree , J. C. , Ilundain , A. A. and Brot‐Laroche , E.Thyroid hormone regulation of the Na+/glucose cotransporter SGLT1 in Caco‐2 cells . Biochem. J. , 334 , 633 – 640 ( 1998. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Mahraoui , L. , Rodolosse , A. , Barbat , A. , Dussaulx , E. , Zweibaum , A. , Rousset , M. and Brot‐Laroche , E.Presence and differential expression of SGLT1, GLUT1, GLUT2, GLUT3 and GLUT5 hexose‐transporter mRNAs in Caco‐2 cell clones in relation to cell growth and glucose consumption . Biochem. J. , 298 , 529 – 633 ( 1994. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Yamamoto , T. , Seino , Y. , Fukumoto , H. , Koh , G. , Yano , H. , Inagaki , N. , Yamada , Y. , Inoue , K. , Manabe , T. and Imura , H.Over‐expression of facilitative glucose transporter genes in human cancer . Biochem. Biophys. Res. Commun. , 170 , 223 – 230 ( 1990 ). [DOI] [PubMed] [Google Scholar]
  • 18.Younes , M. , Brown , R. W. , Mody , D. R. , Fernandez , L. and Laucirica , R.GLUT1 expression in human breast carcinoma: correlation with known prognostic markers . Anti-cancer Res. , 15 , 2895 – 2898 ( 1995. ). [PubMed] [Google Scholar]
  • 19.Younes , M. , Lechago , L. V. and Lechago , J.Overexpres‐sion of the human erythrocyte glucose transporter occurs as a late event in human colorectal carcinogenesis and is associated with an increased incidence of lymph node metastasis . Clin. Cancer Res. , 2 , 1151 – 1154 ( 1996. ). [PubMed] [Google Scholar]
  • 20.Younes , M. , Brown , R. W. , Stephenson , M. , Gondo , M. and Cagle , P. T.Overexpression of Glut1 and Glut3 in Stage I nonsmall cell lung carcinoma is associated with poor survival . Cancer , 80 , 1046 – 1051 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 21.Ogawa , J. , Inoue , H. and Koide , S.Glucose‐transporter‐type‐I‐gene amplification correlates with sialyl‐Lewis‐X synthesis and proliferation in lung cancer . Int. J. Cancer , 74 , 189 – 192 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 22.Flier , J. S. , Mueckler , M. M. , Usher , P. and Lodish , H. F.Elevated levels of glucose transport and transporter messenger RNA are induced by ras or src oncogenes . Science , 235 , 1492 – 1495 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 23.Noguchi , Y. , Okamoto , T. , Marat , D. , Yoshikawa , T. , Saitoh , A. , Doi , C. , Fukuzawa , K. , Tsuburaya , A. , Satoh , S.and Ito T. Expression of facilitative glucose transporter 1 mRNA in colon cancer was not regulated by k‐ras . Cancer Lett. , 154 , 137 – 142 ( 2000. ). [DOI] [PubMed] [Google Scholar]
  • 24.Hiraki , Y. , Rosen , O. M. and Birnbaum , M. J.Growth factors rapidly induce expression of the glucose transporter gene . J. Biol. Chem. , 263 , 13655 – 13662 ( 1988. ). [PubMed] [Google Scholar]
  • 25.Kitagawa , T. , Tanaka , M. and Akamatsu , Y.Regulation of glucose transport activity and expression of glucose transporter mRNA by serum, growth factors and phorbol ester in quiescent mouse fibroblasts . Biochim. Biophys. Acta , 980 , 100 – 108 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 26.Rollins , B. J. , Morrison , E. D. , Usher , P. and Flier , J. S.Platelet‐derived growth factor regulates glucose transporter expression . J. Biol. Chem. , 263 , 16523 – 16526 ( 1988. ). [PubMed] [Google Scholar]
  • 27.Iliopoulos , O. , Levy , A. P. , Jiang , C. , Kaelin , W. G. and Goldberg , M. A.Negative regulation of hypoxia‐inducible genes by the von Hippel‐Lindau protein . Proc. Natl. Acad. Sci. USA , 93 , 10595 – 10599 ( 1996. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Leadle , J. M. , O'Rourke , J. K , Bartlett , S. M. , Poulton , J. and Ratcliffe , P. J.Isoenzyme‐specific regulation of genes involved in energy metabolism by hypoxia: similarities with the regulation of erythropoietin . Biochem. J. , 313 , 809 – 814 ( 1996. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Briasoulis , E. , Judson , I. , Pavlidis , N. , Beale , P. , Wanders , J. , Groot , Y. , Veerman , G. , Schuessler , M. , Niebch , G. , Siamopoulos , K. , Tzamakou , E. , Rammou , D. , Wolf , L. , Walker , R. and Hanauske , A.Phase I trial of 6‐hour infusion of glufosfamide, a new alkylating agent with potentially enhanced selectivity for tumors that overexpress transmembrane glucose transporters: a study of the European Organization for Research and Treatment of Cancer Early Clinical Studies Group . J. Clin. Oncol , 18 , 3535 – 3544 ( 2000. ). [DOI] [PubMed] [Google Scholar]
  • 30.Veyhl , M. , Wagner , K. , Volk , C. , Gorboulev , V. , Baumgarten , K. , Weber , W. M. , Schaper , M. , Bertram , B. , Wiessler , M. and Koepsell , H.Transport of the new che‐motherapeutic agent beta‐D‐glucosylisophosphoramide mustard (D‐19575) into tumor cells is mediated by the Na+‐D‐glucose cotransporter SAAT1 . Proc. Natl. Acad. Sci. USA , 95 , 2914 – 2919 ( 1998. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Shim , H. , Chun , Y. S. , Lewis , B. C. and Dang , C. V.A unique glucose‐dependent apoptotic pathway induced by c‐Myc . Proc. Natl. Acad. Sci. USA , 95 , 1511 – 1516 ( 1998. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Kan , O. , Baldwin , S. A. and Whetton , A. D.Apoptosis is regulated by the rate of glucose transport in an interleukin 3 dependent cell line . J. Exp. Med. , 180 , 917 – 923 ( 1994. ). [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES