Insulin potentiates mitogenic effect of epidermal growth factor on
cultured gastric mucous cells.
Ogihara, Shoji, Masahiko Yamada, Toshihiko Saito, Masayuki Shono, and
Kazuhito Rokutan.
Fourth Department of Internal Medicine, Tokyo Medical College,
Tokyo160, Japan; and Department of Nutrition, School of Medicine, The
University of Tokushima. Tokushima 770, Japan
APStracts 3:0013G, 1996.
Epidermal growth factor (EGF) stimulated proliferation of gastric
mucous epithelial cells from guinea pigs in serum-free culture
conditions. Western blot analysis with anti-phosphotyrosine antibody
showed that EGF initiated tyrosine phosphorylation of a 170
kilodalton protein, and this protein was identical to the EGF
receptor. Insulin was not mitogenic, but it potentiated the mitogenic
effect of EGF. Tyrosine phosphorylation of additional proteins was
not induced by the combined actions of insulin and EGF. Stimulation
by EGF and/or insulin did not cause a calcium response. However, when
insulin was added to cells pretreated with EGF for more than 6 h, it
elicited a rapid [Ca2+]i rise, which was reproducible in both cell
suspension and single cell analyses. This calcium response coincided
with the translocation of protein kinase C (PKC) from the cytosolic
to the particulate fraction. Phorbol 12-myristate 13-acetate also
caused the translocation and stimulated proliferation of the cells.
These results suggest that the calcium-dependent activation of PKC
may participate in the potentiation of the mitogenic effect of EGF by
insulin.
Received 10 August 1993; accepted in final form 26 December 1995.
APS Manuscript Number G317-3.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 22 January 96