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Endocrinology Vol. 142, No. 1 121-128
Copyright © 2001 by The Endocrine Society

ARTICLES

Somatostatin Inhibits Akt Phosphorylation and Cell Cycle Entry, But Not p42/p44 Mitogen-Activated Protein (MAP) Kinase Activation in Normal and Tumoral Pancreatic Acinar Cells1

Stéphanie Charland, Marie-Josée Boucher, Mathieu Houde and Nathalie Rivard2

Département d’Anatomie et Biologie Cellulaire, Faculté de Médecine, Université de Sherbrooke, Sherbrooke (Québec), J1H 5N4, Canada

Address all correspondence and requests for reprints to: Dr. Nathalie Rivard, Département d’Anatomie et de Biologie Cellulaire, Faculté de Médecine, Université de Sherbrooke, Sherbrooke, QC, J1H5N4, Canada. E-mail: nrivard{at}courrier.usherb.ca

Somatostatin, or its structural analog SMS 201–995 (SMS), is recognized to exert a growth-inhibitory action in rat pancreas, but the cellular mechanisms are not completely understood. This study was undertaken to evaluate the effect of SMS on p42/p44 MAP kinases and phosphatidylinositol 3-kinase activation and to analyze expression of some cell cycle regulatory proteins in relation to pancreatic acinar cell proliferation in vivo (rat pancreas), as well as in the well-established tumoral cell line AR4–2J. We herein report that: 1) SMS inhibits caerulein-induced pancreatic weight and DNA content and abolishes epidermal growth factor (EGF)-stimulated AR4–2J proliferation; 2) SMS only moderately reduces the stimulatory effect of caerulein on p42/p44 MAP kinase activities in pancreas and has no effect on EGF-stimulated MAP kinase activities in AR4–2J cells; 3) SMS repressed caerulein-induced Akt activity in normal pancreas; 4) SMS has a strong inhibitory action on cyclin E expression induced by caerulein in pancreas and EGF in AR4–2J cells and as expected, the resulting cyclin E-associated cyclin-dependent kinase (cdk)2 activity, as well as pRb phosphorylation, are blunted by SMS treatment in both models; and 5) SMS suppresses mitogen-induced p27Kip1 down-regulation, as well as marginally induces p21Cip expression. Thus, our data suggest that somatostatin-induced growth arrest is mediated by inhibition of phosphatidylinositol 3-kinase pathway and by enhanced expression of p21Cip and p27Kip1, leading to repression of pRb phosphorylation and cyclin E-cdk2 complex activity.




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