Expression of insulin-like growth factor ii (igf-ii) and igf
binding proteins in differentiating human intestinal caco-2
cells.
Zhang, Yan, Debra A. Wick, Bellur Seetharam, and Nancy M. Dahms.
Department of Biochemistry (Y.Z., D.A.W., B.S., N.M.D.) and
Department of Medicine, Division of Gastroenterology, Medical College
of Wisconsin, Milwaukee, Wisconsin 53226
APStracts 2:0119E, 1995.
The mitogenic and metabolic effects of insulin-like growth factor II
(IGF-II) can be modulated by six distinct IGF binding proteins
(IGFBPs). As a first step towards understanding the role of IGFs and
their binding proteins in intestinal epithelial cell differentiation,
the expression of IGF-II and IGFBPs was characterized in the human
colon adenocarcinoma Caco-2 cell line. Northern blot analysis
revealed two IGF-II transcripts of 5.4 and 4.5 kb and ribonuclease
protection assays indicated that IGF-II mRNA levels are regulated
during Caco-2 differentiation. A specific radioimmunoassay detected
IGF-II in serum-free conditioned medium, the level of which was 3-5
-fold higher in proliferating cells than in differentiated cells.
Immunoprecipitation and ligand blot analyses of conditioned medium
demonstrated that IGFBP-2, -3, -4, and -6 are synthesized by Caco-2
cells, with IGFBP-2 and IGFBP-4 being the major IGFBPs secreted, and
that the levels of IGFBP-2 and IGFBP-6 decreased as differentiation
proceeded. These results indicate that the expression of IGF-II,
IGFBP-2, and IGFBP-6 is regulated in a differentiation-dependent
manner in Caco-2 cells.
Received 29 December 1994; accepted in final form 3 February
1995.
APS Manuscript Number E535-4.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 May 1995.