简介：

简介：它一致地被看了那oncoproteinp28GANK，它是在人的hepatocellular癌(HCC)的overexpressed，在HCC的tumorigenesis起一个关键作用。然而，内在的机制仍然保持不清楚。这里，我们证明p28GANK在endoplasmic蜂窝胃导致的HCC房间禁止apoptosis(嗯)应力。在期间嗯应力，p28GANK提高展开的蛋白质反应，支持嗯从翻译压抑的恢复，并且从而便于房间的能力应付压力条件。而且，p28GANKupregulates调整葡萄糖的蛋白质78(GRP78)，一把钥匙嗯女伴蛋白质，它随后提高合拢能力的ER并且支持恢复从嗯应力。我们也证明p28GANK增加p38激活mitogen的蛋白质kinase和Aktphosphorylation，并且禁止原子因素kappaB(NF-B)激活在下面嗯强调upregulation，它接着贡献GRP78。一起拿，我们的结果显示p28GANK禁止嗯在HCC房间的导致压力的apoptosis，至少部分地，由提高适应反应和GRP78表示。我们建议p28GANK在ER压力条件下面为HCC前进有潜在的含意。

简介：

简介：Amurinemacrophage-likecelllineJ774,acquired,inresponsetoLPS,anabilitytokilltumornecrosisfactor(TNF)-insensitivetargetP815mastocytomacellswhereasanothercellline,P388D1didnot,LPStriggeredsignalingmechanismsbetweenthetwocelllineswerecomparedwithanaimtoinquireaboutthepossiblenatureoftheabove-mentioneddifference,TheresultswhowedthattwocelllinesrespondtoLPS-treatmentbyparallelactivationofbothphospholipasesCandA2(PLCandPLA2)toapproximatelythesameextent.ThemaximumresponseoftothenzymesofJ774cellswasnotedwithin10minthetreatmentwhereasthatofP388D1cellsrequiredmorethan20min,TheotherpropertiesofLPS-responsiveenzymesstudiedweresimilarbetweentwocelllines,includingActivationofPLCandPLA2andPKCinmacrophagesbyLPS.Ca2+augmentationofenzymeactivation,participationofguaninenucleotidebinding(G)proteinsintheinitialactivationpreocesses,andinhibitionofenzymeactivationbythepriortreatmentofcellswithcholeraorpertussistoxinsetc.Moreover,LPS-triggeredactivationofPLCandPLA2wasfoundtobefollowedbytheincreaseofPKCactivitiesinbothcelllines.Inspiteofthesesimilarities.J774cellspossessedbothbasicandacidicformsofPKCactivities,whileP388D1cellsownedonlyPKCofbasicform,Nevertheless,thequestionwhyJ774cellsbutnotP388D1cells,canacquirethetumoricidalactivity,aganistP815,cellsfollowingLPStreatmentrematinstobeanswered.

简介：Amurinemacrophage-likecellline,J774,acquried,inresponsetoLPS,anabilitytokilltumornecrosisfactor（TNF）-insensitivetargetP815mastocytomacells,whereasanothercellline,P388D1,didnot.LPS-triggeredsignalingmechanismsbetweenthetwocelllineswerecomparedwithanaimtoinquireaboutthepossiblenatureoftheabove-mentioneddifference.TheresultsshowedthattwocelllinesrespondtoLPS-treatmentbyparallelactivationofbothphospholipasesCandA2（PLCandPLA2）toapproximatelythesameextent.ThemaximumresponseofbothenzymesofJ774cellswasnotedwithin10minofthetreatment,whereasthatofP388D1cellsrequiredmorethan20min.TheotherpropertiesofLPS-responsiveenzymesstudiedweresimilarbetweentwocelllines,ineludingActivationofPLCandPLA2andPKCinmacrophagesbyLPSCa2+augmentationofenzymeactivation,participationofguaninenucleotidebinding（G）proteinsintheinitialactivationprocesses,andinhibitionofenzymeactivationbythepriortreatmentofcellswithcholeraorpartussistoxinsetc.Moreover,LPS-triggeredactivationofPLCandPLA2wasfoundtobefollowedbytheincreaseofPKCactivitiesinbothcelllines.Inspiteofthesesimilarities,J774cellspossessedbothbasicandacidicformsofPKCactivities,whileP388D1cellsownedonlyPKCofbasicform.Nevertheless,thequestionwhyJ774cells,butnotP388D1cells,canacquirethetumoricidalactiyity,aganistP815cellsfollowingLPS-treatmentremainstobeanswered.

简介：OverexpressionandactivationofHER-2/neu(alsoknownasc-erbB-2),aproto-oncogene,wasfoundinabout30%ofhumanbreastcancers,promotingcancergrowthandmakingcancercellsresistanttochemo-andradio-therapy.Wild-typep53iscrucialinregulatingcellgrowthandapoptosisandisfoundtobemutatedordeletedin60-70%ofhumancancers.Andsomecancerswithawild-typep53donothavenormalp53function,suggestingthatitisimplicatedinacomplexprocessregulatedbymanyfactors.Inthepresentstudy,weshowedthattheoverexpressionofHER-2/neucoulddecreasetheamountofwild-typep53proteinviaactivatingPI3Kpathway,aswellasinducingMDM2nucleartranslocationinMCF7humanbreastcancercells.BlockageofPI3KpathwaywithitsspecificinhibitorLY294002causedG1-Sphasearrest,decreasedcellgrowthrateandincreasedchemo-andradio-therapeuticsensitivityinMCF7cellsexpressingwild-typep53.However,itdidnotincreasethesensitivitytoadriamycininMDA-MB-453breastcancercellscontainingmutantp53.OurstudyindicatesthatblockingPI3KpathwayactivationmediatedbyHER-2/neuoverexpressionmaybeusefulinthetreatmentofbreasttumorswithHER-2/neuoverexpressionandwild-typep53.