Deregulation of hexose transporter expression in caco-2 cells by ras and polyoma middle t oncogenes. Baron-Delage, Sophie, Lahcen Mahraoui, Axelle Cadoret, Danielle Veissiere, Jean-Louis Taillemite, Eric Chastre, Christian Gespach, Alain Zweibaum, Jacqueline Capeau, Edith Brot-Laroche, and Gis[grave]ele Cherqui. Laboratoire de Biologie Cellulaire, INSERM U. 402, Facult[acute]e de M[acute]edecine Saint-Antoine, 27 rue Chaligny, 75571 Paris C[acute]edex 12 (France), INSERM U. 178, 16 avenue Paul Vaillant Couturier, 94807 Villejuif C[acute]edex (France), Laboratoire de Cytog[acute]en[acute]etique and INSERM U. 55, H[circumflex]opital Saint-Antoine, 184 rue du Faubourg Saint-Antoine, 75571 Paris C[acute]edex 12 (France)
APStracts 2:0239G, 1995.
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 GLUT2, GLUT5 and SGLT1 transporters in addition to GLUT1 and GLUT3. Along with increased glucose consumption rates, both oncogene -transfected cells exhibited increased levels of GLUT1 and GLUT3 mRNAs and/or immunoreactive proteins as compared with control vector Caco-2 cells. In contrast, oncogene-transfected cells lost GLUT2, GLUT5 and SGLT1 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 GLUT1 and GLUT3 expression, and 2) repression of GLUT2, GLUT5 and SGLT1 which parallels repression of some markers of the enterocyte -like differentiated phenotype of Caco-2 cells. 

Received 17 February 1995; accepted in final form 8 August 1995.
APS Manuscript Number G71-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95