Deregulation of hexose transporter expression in Caco-2 cells by ras and polyoma middle T oncogenes.
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.
Baron-Delage
S
S
Laboratoire de Biologie Cellulaire, Institut National de la Santé et de la Recherche Médicale Unité 402, Faculté de Médicine Saint-Antoine, Paris, France.
Mahraoui
L
L
Cadoret
A
A
Veissiere
D
D
Taillemite
J L
JL
Chastre
E
E
Gespach
C
C
Zweibaum
A
A
Capeau
J
J
Brot-Laroche
E
E
Cherqui
G
G
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
D000952:Antigens, Polyomavirus Transforming; D015415:Biomarkers; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; C495674:SLC5A1 protein, human; D051269:Sodium-Glucose Transporter 1