AJP - Gastrointestinal and Liver Physiology, Vol 270, Issue 2 314-G323, Copyright © 1996 by American Physiological Society
Deregulation of hexose transporter expression in Caco-2 cells by ras and polyoma middle T oncogenes
S. Baron-Delage, L. Mahraoui, A. Cadoret, D. Veissiere, J. L. Taillemite, E. Chastre, C. Gespach, A. Zweibaum, J. Capeau, E. Brot-Laroche and G. Cherqui
Laboratoire de Biologie Cellulaire, Institut National de la Sante et de la Recherche Medicale Unite 402, Faculte de Medicine Saint-Antoine, Paris, France.
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.
