Octreotide, a somatostatin analogue, mediates its antiproliferative action in pituitary tumor cells by altering phosphatidylinositol 3-kinase signaling and inducing Zac1 expression.

Somatostatin limits cell growth by inhibiting the proliferative activity of growth factor receptors. In this study, it is shown that in pituitary tumor cells, the somatostatin analogue octreotide produces its antiproliferative action by inducing the expression the tumor suppressor gene Zac1. ZAC/Zac1 induces cell cycle arrest and apoptosis and is highly expressed in normal pituitary, mammary, and ovarian glands but is down-regulated in pituitary, breast, and ovarian tumors. Knocking down Zac1 by RNA interference abolished the antiproliferative effect of octreotide in pituitary tumor cells, indicating that Zac1 is necessary for the action of octreotide. The effect of octreotide on Zac1 expression was pertussis toxin sensitive and was abolished after transfection with a dominant negative vector for SHP-1. Zac1 is a target of the phosphatidylinositol 3-kinase (PI3K) survival pathway. Octreotide treatment decreased the tyrosine phosphorylation levels of the PI3K regulatory subunit p85, induced dephosphorylation of phosphoinositide-dependent kinase 1 (PDK1) and Akt, and activated glycogen synthase kinase 3beta (GSKbeta). Therefore, in pituitary tumor cells, somatostatin analogues produce their antiproliferative action by acting on the PI3K/Akt signaling pathway and increasing Zac1 gene expression.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Surfactant Monolayer Bending Elasticity in Lipase Containing Bicontinuous Microemulsions

Lipase-catalyzed reactions offer many advantages among which a high degree ofselectivity combined with the possibility to convert even non-natural substrates are of particular interest. A major drawback in the applicability of lipases in the conversionof synthetically interesting, non-natural substrates is the substantial insolubility of suchsubstrates in water. The conversion of substrates, natural or non-natural, by lipasesgenerally involves the presence of a water–oil interface. In the present paper, we exploit the fact that the presence of lipases, in particular the lipase from Candidaantarctica B (CalB), changes the bending elastic properties of a surfactant monolayerin a bicontinuous microemulsion consisting of D2O/NaCl -n-(d)-octane-pentaethyleneglycol monodecyl ether (C10E5) in a similar manner as previously observed for amphiphilic block-copolymers. To determine the bending elastic constant, we have used twoapproaches, small angle neutron scattering (SANS) and neutron spin echo (NSE)spectroscopy. The time-averaged structure from SANS showed a slight decrease inbending elasticity, while on nanosecond time scales as probed with NSE, a stiffening has been observed, which was attributed to adsorption/desorption mechanisms of CalB atthe surfactant monolayer. The results allow to derive further information on the influence of CalB on the composition and bending elasticity of the surfactant monolayer itself aswell as the underlying adsorption/desorption mechanism