American Association of Endocrine Surgeons| Volume 128, ISSUE 6, P946-951, December 2000

Strategy for identification of novel glucose transporter family members by using internet-based genomic databases


      Background. We previously reported that medullary thyroid carcinomas and pheochromocytomas avidly take up the glucose analog fluoro-deoxyglucose on positron emission tomography but do not express any of the known human facilitative glucose transporters. We therefore hypothesized that a novel glucose transporter is responsible for glucose uptake in these tumors. Methods. Internet-based Expressed Sequence Tags and high throughput genome sequence databases were screened for novel sequences homologous to the known glucose transporters. Derived clones were used to screen cDNA libraries. Sequence comparison and hydropathic analysis of the putative proteins were performed. Results. We identified 2 novel genes (GLUT8 and GLUT9) that are members of the facilitative glucose transporter family. The putative GLUT8 and GLUT9 proteins have 44% and 31% sequence identity to GLUT5 and GLUT3, respectively. Hydropathic analysis showed both have exofacial and transmembrane domains consistent with a hexose transporter. Conclusions. By using the Expressed Sequence Tags database, we identified novel members of the glucose transporter family. Further work will establish function and expression patterns in medullary thyroid carcinomas and pheochromocytomas. Internet-based genomic databases allow rapid screening and identification of candidate sequences of novel members of human gene families.(Surgery 2000;128:946-51.)
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        • Warburg O
        The metabolism of tumors.
        : Constable, London1930
        • smith ta
        fdg uptake, tumour characteristics and response to therapy: a review.
        nucl med commun. 1998; 19: 97-105
        • Musholt TJ
        • Musholt PB
        • Dehdashti F
        • Moley JF
        Evaluation of fluorodeoxyglucose-positron emission tomographic scanning and its association with glucose transporter expression in medullary thyroid carcinoma and pheochromocytoma: a clinical and molecular study.
        Surgery. 1997; 122: 1049-1061
        • Hediger MA
        • Rhoads DB
        Molecular physiology of sodiumglucose cotransporters.
        Physiol Rev. 1994; 74: 993-1026
        • Mueckler M
        Facilitative glucose transporters.
        Eur J Biochem. 1994; 219: 713-725
        • Kayano T
        • Burant CF
        • Fukumoto H
        • Gould GW
        • Fan YS
        • Eddy RL
        • et al.
        Human facilitative glucose transporters: isolation, functional characterization, and gene localization of cDNAs encoding an isoform (GLUT5) expressed in small intestine, kidney, muscle, and adipose tissue and an unusual glucose transporter pseudogene-like sequence (GLUT6).
        J Biol Chem. 1990; 265: 13276-13282
        • Burchell A
        A re-evaluation of GLUT 7 [letter].
        Biochem J. 1998; 331: 973
        • Brown RS
        • Leung JY
        • Fisher SJ
        • Frey KA
        • Ethier SP
        • Wahl RL
        Intratumoral distribution Of tritiated-Fdg in breast carcinoma: correlation between GLUT-1 expression and Fdg uptake.
        J Nucl Med. 1996; 37: 1042-1047
        • Waki A
        • Kato H
        • Yano R
        • Sadato N
        • Yokoyama A
        • Ishii Y
        • et al.
        The importance of glucose transport activity as the ratelimiting step of 2-deoxyglucose uptake in tumor cells in vitro.
        Nucl Med Biol. 1998; 25: 593-597
        • Younes M
        • Lechago LV
        • Somoano JR
        • Mosharaf M
        • Lechago J
        Wide expression of the human erythrocyte glucose transporter GLUT1 in human cancers.
        Cancer Res. 1996; 56: 1164-1167
        • Brown RS
        • Wahl RL
        Overexpression of GLUT-1 glucose transporter in human breast cancer: an immunohistochemical study.
        Cancer. 1993; 72: 2979-2985
        • Boguski MS
        • Lowe TM
        • Tolstoshev CM
        dbEST—database for “expressed sequence tags” [letter].
        Nat Genet. 1993; 4: 332-333
        • Burge C
        • Karlin S
        Prediction of complete gene structures in human genomic DNA.
        J Mol Biol. 1997; 268: 78-94
        • Ibberson M
        • Uldry M
        • Thorens B
        GLUTX1, a novel mammalian glucose transporter expressed in the central nervous system and insulin-sensitive tissues.
        J Biol Chem. 2000; 275: 4607-4612
        • Appel RD
        • Bairoch A
        • Hochstrasser DF
        A new generation of information retrieval tools for biologists: the example of the ExPASy WWW server.
        Trends Biochem Sci. 1994; 19: 258-260
        • Sonnhammer ELL
        • von Heijne G
        • Krogh A
        A hidden Markov model for predicting transmembrane helices in protein sequences.
        in: Sixth international conference on intelligent systems for molecular biology. : AAAI Press, Menlo Park (CA)1998: 175-182
        • Kozak M
        Interpreting cDNA sequences: some insights from studies on translation.
        Mamm Genome. 1996; 7: 563-574
        • Phay J
        • Hussain H
        • Moley J
        Cloning and expression analysis of a novel member of the facilitative glucose transporter family.
        Genomics. 2000; 66: 217-220
        • Thorens B
        Glucose transporters in the regulation of intestinal, renal, and liver glucose fluxes.
        Am J Physiol. 1996; 270: G541-G553