title: Deregulation of hexose transporter expression in Caco-2 cells by ras and polyoma middle T oncogenes.
abstract: We investigated whether the oncogenic activation of p21ras or pp60c-src, which is frequently observed in colorectal cancers, induced alterations of sugar uptake in human colonic cells. We therefore examined hexose transporter expression and/or activity in Caco-2 cells transfected either with an activated human (Val-12) Ha-ras gene or with the polyoma middle T (PyMT) oncogene, a constitutive activator of pp60c-src tyrosine kinase activity. Experiments were performed at day 20 of culture, when Caco-2 cells express enterocyte-specific GLUT-2, GLUT-5, and SGLT-1 transporters in addition to GLUT-1 and GLUT-3. Along with increased glucose consumption rates, both oncogene-transfected cells exhibited increased levels of GLUT-1 and GLUT-3 mRNAs and/or immunoreactive proteins compared with control vector Caco-2 cells. In contrast, oncogene-transfected cells lost GLUT-2, GLUT-5, and SGLT-1 expression as determined by Northern and/or Western blot analyses and/or specific transport assays. The oncogene-induced repressive effect on these enterocyte-specific hexose transporters extended to brush-border hydrolases and villin but not to tight junctional protein ZO-1. In conclusion, oncogenic p21ras and PyMT/pp60c-src induce severe deregulation of hexose transporter expression in Caco-2 cells, which is manifested by 1) increased GLUT-1 and GLUT-3 expression and 2) repression of GLUT-2, GLUT-5, and SGLT-1, which parallels repression of some markers of the enterocyte-like differentiated phenotype of Caco-2 cells.
authors.affiliation: Laboratoire de Biologie Cellulaire, Institut National de la Santé et de la Recherche Médicale Unité 402, Faculté de Médicine Saint-Antoine, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Baron-Delage
authors.forename: L
authors.initials: L
authors.lastname: Mahraoui
authors.forename: A
authors.initials: A
authors.lastname: Cadoret
authors.forename: D
authors.initials: D
authors.lastname: Veissiere
authors.forename: J L
authors.initials: JL
authors.lastname: Taillemite
authors.forename: E
authors.initials: E
authors.lastname: Chastre
authors.forename: C
authors.initials: C
authors.lastname: Gespach
authors.forename: A
authors.initials: A
authors.lastname: Zweibaum
authors.forename: J
authors.initials: J
authors.lastname: Capeau
authors.forename: E
authors.initials: E
authors.lastname: Brot-Laroche
authors.forename: G
authors.initials: G
authors.lastname: Cherqui
mesh_terms: D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D015415:Biomarkers; D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000502:physiology; D011905:Genes, ras; D006801:Humans; D007422:Intestines / Q000166:cytology; D008562:Membrane Glycoproteins / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009857:Oncogenes; D051269:Sodium-Glucose Transporter 1
chemical_list: D000952:Antigens, Polyomavirus Transforming; D015415:Biomarkers; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; C495674:SLC5A1 protein, human; D051269:Sodium-Glucose Transporter 1