Disease relevance of SLC2A5

• Expression of the fructose transporter GLUT5 in human breast cancer [1].
• GLUT5 was detected in 27% of breast and colon adenocarcinoma, liver carcinoma, lymphomas, and testis seminoma samples [2].
• The effect of cyclic AMP on the expression of the fructose transporter, GLUT5, was studied in Caco-2 cells, a human colon cancer cell line that differentiates spontaneously in culture into cells with the properties of small intestine enterocytes [3].
• Moreover, using a recombinant adenovirus expression system, we expressed a GLUT5 (N terminus approximately TM6)-GLUT1(IL)-GLUT5(TM7 approximately C-terminus) chimera, which was observed at the basolateral membrane [4].
• Expression of GLUT 1 through GLUT 5 was examined by Western blot analysis of tumor tissue from eight of the patients evaluated and an additional panel of 10 MTCs and seven pheochromocytomas [5].

High impact information on SLC2A5

• Molecular analysis of the fructose transporter gene (GLUT5) in isolated fructose malabsorption [6].
• Functional properties and tissue distribution of GLUT5 suggest that IFM might be due to mutations in the GLUT5 gene [6].
• The intestinal absorption of fructose is carried out by the facilitative hexose transporter, which has been designated as GLUT5 [6].
• In addition, sequence analysis of each of the 12 GLUT5 exons was performed in the index case and confirmed the negative single-strand conformation polymorphism findings [6].
• Identification of a high-affinity fructose transporter on human breast cancer cells opens opportunities to develop novel strategies for early diagnosis and treatment of breast cancer [1].

Chemical compound and disease context of SLC2A5

• We also found that the breast cancer cell lines transport fructose and express the fructose transporter GLUT5 [1].
• Differential subcellular distribution of glucose transporters GLUT1-6 and GLUT9 in human cancer: Ultrastructural localization of GLUT1 and GLUT5 in breast tumor tissues [2].
• The results imply an alternative way in treating breast tumor as the AS against Glut5, unlike tamoxifen, takes effect on breast tumor cells via suppressing the expression of Glut5 that they specifically possess, and regardless whether the breast tumors are estrogen dependent or not [7].

Biological context of SLC2A5

• The gene encoding the GLUT5 protein is located on the short arm of human chromosome 1 [8].
• However, if a protein kinase A inhibitor was used to block cAMP signalling, extensive GLUT5 mRNA degradation was observed, with no change in basal transcription levels demonstrating the involvement of cAMP in GLUT5 mRNA stability [9].
• The biochemical properties and tissue distribution of GLUT5 are consistent with a physiological role for this protein as a fructose transporter [10].
• To define its role in sugar transport, human GLUT5 was expressed in Xenopus oocytes and its substrate specificity and kinetic properties determined [10].
• The aim of this study was to investigate the gene expression levels of the GLUT family, especially GLUT1, GLUT3, and GLUT5 in primary lung cancer, metastatic liver tumors, and normal lung tissues, and to compare the expression levels of primary and metastatic tumors with those of normal tissues [11].

Anatomical context of SLC2A5

• GLUT5 mRNA is expressed at highest levels in small intestine and at much lower levels in kidney, skeletal muscle, and adipose tissue [8].
• Expression of in vitro synthesized human GLUT5 mRNA in Xenopus laevis oocytes indicates that the GLUT5 protein is a cytochalasin B-sensitive glucose carrier [8].
• 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) [8].
• Glut5 is a fructose transporter that is abundant in spermatozoa and the apical membrane of intestinal cells [12].
• RESULTS: Using PCR we detected transcripts for eight glucose transporter isoforms (GLUTs 1, 3, 6, 8, 9, 10, 11 and 12) and for a fructose transporter (GLUT5) in human articular cartilage [13].

Associations of SLC2A5 with chemical compounds

• The role for high levels of the fructose transporter GLUT 5 in macrophages and foam cells is unknown since interstitial and circulating fructose concentrations are low in these cells [14].
• Regulation of expression of the human fructose transporter (GLUT5) by cyclic AMP [3].
• Treatment of differentiated Caco-2 cells with 50 microM forskolin, which stimulates adenylate cyclase and raises intracellular cyclic AMP levels, increased fructose uptake 2-fold and raised GLUT5 protein and mRNA levels 5- and 7-fold respectively [3].
• The localization of GLUT5 to the luminal surface of mature absorptive epithelial cells implies that this protein participates in the uptake of dietary sugars [15].
• Overexpression of GLUT5 in Diabetic Muscle Is Reversed by Pioglitazone [16].

Physical interactions of SLC2A5

• GLUT11 (SLC2A11) is a class II sugar transport facilitator which exhibits highest similarity with the fructose transporter GLUT5 (about 42%) [17].

Regulatory relationships of SLC2A5

• Immunohistochemical study revealed that the GLUT5 protein expressed was localized at apical membranes and that the GLUT1 expressed was present primarily in the basolateral membranes of cells grown on permeable support [4].
• Fructose-induced changes in FBPase activity may regulate changes in GLUT5 expression and activity in the small intestine of neonatal rats [18].

Other interactions of SLC2A5

• Immunoblots of muscle homogenates verified that the respective proteins for GLUT4, GLUT5, and GLUT12 were present in normal human muscle [19].
• Immunofluorescent studies demonstrated that GLUT4 and GLUT12 were predominantly expressed in type I oxidative fibers; however, GLUT5 was expressed predominantly in type II (white) fibers [19].
• We conclude that the post-transcriptional regulation of GLUT5 by fructose involves increases in mRNA stability mediated by the cAMP pathway and Paip2 (PABP-interacting protein 2) binding [9].
• Fructose modulates GLUT5 mRNA stability in differentiated Caco-2 cells: role of cAMP-signalling pathway and PABP (polyadenylated-binding protein)-interacting protein (Paip) 2 [9].
• Currently, there are five established functional facilitative glucose transporter isoforms (GLUT1-4 and GLUTX1), with GLUT5 being a fructose transporter [20].

Analytical, diagnostic and therapeutic context of SLC2A5

• Reassignment of SLC2A5 to 1p36.2 was confirmed by somatic cell and radiation hybrid mapping panels and was consistent with previous EST mapping data [21].
• Immunoblotting and immunolocalization experiments identified the presence of GLUT1 and GLUT5 as the main facilitative hexose transporters expressed in human erythrocytes, with GLUT2 present in lower amounts [22].
• In situ RT-PCR and ultrastructural immunohistochemistry confirmed GLUT5 expression in breast cancer [2].
• Immunohistochemical analysis of adult small intestine localized GLUT5 to the luminal surface of mature enterocytes, a finding confirmed by Western blot analysis of purified human jejunal brush-border membranes [15].
• This was associated with threefold increases in SGLT1 and GLUT5 mRNA measured by Northern blotting [23].

References