@entity10158 mutations at codon 209 have been recently identified in approximately 50% of @entity2184 ( @entity2184 ) and are reported to be oncogenic through activating the MAPK/ @entity1366 pathway. @entity7131 ( @entity7131 ) is a component of signaling from @entity10158 to @entity1366 . Inhibition of @entity7131 might regulate @entity10158 mutation-induced @entity1366 activation, resulting in growth inhibition of @entity2184 cells carrying @entity10158 mutations. @entity2184 cells carrying wild type or mutant @entity10158 were treated with the @entity7131 inhibitor @entity22988 . Effects on proliferation, apoptosis, and signaling events were evaluated. @entity22988 downregulated the expression of several @entity7131 isoforms including PKCbII @entity7131  , @entity7131   and/or their phosphorylation in @entity10158 mutated cells. Downregulation of these @entity7131 isoforms in @entity10158 mutated cells by shRNA resulted in reduced viability. @entity22988 exhibited greater antiproliferative effect on @entity10158 mutant cells than wild type cells through induction of G1 arrest and apoptosis. @entity22988 -induced G1 arrest was associated with inhibition of @entity1366 phosphorylation, downregulation of @entity4910 , and accumulation of cyclin dependent kinase inhibitor @entity5438 ( @entity13525 ). Furthermore, @entity22988 reduced the expression of antiapoptotic @entity588 and survivin in @entity10158 mutant cells. Inhibition of @entity1366 phosphorylation with a MEK specific inhibitor enhanced the sensitivity of @entity10158 wild type cells to @entity22988 , accompanied by @entity5438 ( @entity13525 ) accumulation and/or inhibition of @entity22988 -induced survivin and @entity588 upregulation. @entity7131 inhibitors such as @entity22988 have activity against @entity2184 cells carrying @entity10158 mutations through inhibition of the @entity7131 / @entity1366 pathway and induction of G1 arrest and apoptosis. Inhibition of the @entity7131 pathway provides a basis for clinical investigation in @entity1 with @entity2184 .

The protein kinase C inhibitor XXXX exhibits antitumor activity against @entity2184 .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity588 :: ('596', 'Gene') :: ['Bcl-2'] @entity10158 :: ('2776', 'Gene') :: ['GNAQ'] @entity5438 :: ('3429', 'Gene') :: ['p27'] @entity4910 :: ('595', 'Gene') :: ['cyclin D1'] @entity7131 :: ('MESH:D020151', 'Disease') :: ['PKC', 'Protein kinase C'] @entity2184 :: ('MESH:C536494', 'Disease') :: ['UM', 'uveal melanomas'] @entity22988 :: ('MESH:C504878', 'Chemical') :: ['enzastaurin', 'Enzastaurin'] @entity13525 :: ('1027', 'Gene') :: ['Kip1'] @entity1366 :: ('5595;5594', 'Gene') :: ['Erk1/2']
@entity22988 :: (MESH:C504878,Chemical) :: ['enzastaurin']
