AJP - Endocrinology and Metabolism, Vol 272, Issue 5 E769-E774, Copyright © 1997 by American Physiological Society
Involvement of MAP kinase and c-fos signaling in the inhibition of cell growth by somatostatin
H. Yoshitomi, Y. Fujii, M. Miyazaki, N. Nakajima, N. Inagaki and S. Seino
Division of Molecular Medicine, Chiba University School of Medicine, Japan.
Somatostatin significantly suppressed cell growth of the mouse
insulinoma-derived cell line MIN6. MIN6 cells exhibited high-affinity
binding of somatostatin with 50% inhibitory concentration value of 0.9 nM.
RNA blot analysis revealed that MIN6 cells expressed only SSTR3 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. Mitogen-activated protein (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), whereas 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.
