Involvement of map kinase/c-fos signaling in the inhibition of cell
growth by somatostatin in insulinoma-derived cells.
Yoshitomi, Hideyuki, Yasukazu Fujii, Masaru Miyazaki, Nobuyuki
Nakajima, Nobuya Inagaki, and Susumu Seino.
Division of Molecular Medicine, Center for Biomedical Science, and
First Department of Surgery, Chiba University School of Medicine;
Chiba 260, Japan
APStracts 4:0023E, 1997.
Somatostatin significantly suppressed cell growth of the mouse
insulinoma-derived cell line MIN6. MIN6 cells exhibited high affinity
binding of somatostatin with IC50 value of 0.9 nM. RNA blot analysis
revealed that MIN6 cells expressed only sst3, among the five
somatostatin receptors so far identified. Treatment of MIN6 cells
with somatostatin significantly reduced the serum-induced c-fos
expression levels. On the other hand, somatostatin (100 nM) treatment
of MIN6 cells cultured in medium containing 10% serum transiently
increased c-fos expression levels to 282 +/- 4.7%, and then
significantly decreased them to 27 +/- 7.6% of the levels before
treatment. MAP kinase activity transiently increased to 656 +/-
91.2%, and decreased thereafter to 39 +/- 13.3% of the activity
before the addition of somatostatin (100 nM) into the medium. In
addition, the stimulatory effect of somatostatin on c-fos expression
and MAP kinase activity (early effect) was not altered by pertussis
toxin (PTX), while the suppressive effect of somatostatin on c-fos
expression and MAP kinase activity (late effect) was mitigated by
PTX. These findings suggest that an inhibition of c-fos expression
mediated by cross-talk between PTX-sensitive G protein signaling and
receptor tyrosine kinase signaling is one of the mechanisms by which
somatostatin inhibits cell growth in MIN6 cells.
Received 21 October 1996; accepted in final form 30 December
1996.
APS Manuscript Number E518-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 19 February 1997