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《膜突蛋白促進(jìn)乳腺癌細(xì)胞侵襲轉(zhuǎn)移的機(jī)制研究.pdf》由會(huì)員上傳分享,免費(fèi)在線閱讀,更多相關(guān)內(nèi)容在應(yīng)用文檔-天天文庫(kù)。
1、復(fù)里虧搪醫(yī)學(xué)版FudanUnivMedSciZ,,U)13N。u.‘,’4葉。u(6u)679UnivJMed膜突蛋白促進(jìn)乳腺癌細(xì)胞侵襲轉(zhuǎn)移的機(jī)制研究倪翔邵志敏(復(fù)旦大學(xué)附屬腫瘤醫(yī)院乳腺外科上海200032)【摘要】目的探討膜突蛋白與乳腺癌細(xì)胞侵襲轉(zhuǎn)移的關(guān)系。方法應(yīng)用免疫組織化學(xué)法、RT—PCR和Westernblot等技術(shù),檢測(cè)轉(zhuǎn)移與非轉(zhuǎn)移性乳腺癌組織以及不同轉(zhuǎn)移潛能人乳腺癌細(xì)胞系中膜突蛋白的定位及表達(dá);應(yīng)用RNAi技術(shù)結(jié)合體外侵襲運(yùn)動(dòng)實(shí)驗(yàn),探討膜突蛋白缺失對(duì)乳腺癌細(xì)胞侵襲運(yùn)動(dòng)能力的影響及相關(guān)分子機(jī)制。結(jié)果免疫組織化學(xué)結(jié)果顯示,膜突蛋白定位于細(xì)胞膜與細(xì)胞質(zhì)
2、,且在轉(zhuǎn)移組中的表達(dá)高于非轉(zhuǎn)移組,差異具有統(tǒng)計(jì)學(xué)意義(P=0.001,=17.536)。Westernblot結(jié)果顯示,膜突蛋白的表達(dá)與乳腺癌細(xì)胞轉(zhuǎn)移潛能呈正相關(guān)。此外,Transwell實(shí)驗(yàn)結(jié)果顯示,膜突蛋白表達(dá)缺失顯著抑制了乳腺癌細(xì)胞的侵襲和遷移能力,且對(duì)侵襲潛能高的乳腺癌細(xì)胞的抑制更為顯著。膜突蛋白缺失后,細(xì)胞中MTDHmRNA與nm-23mRNA水平明顯降低;vimentin蛋白表達(dá)增加、E—cadherin和MMP一9蛋白表達(dá)降低,差異具有統(tǒng)計(jì)學(xué)意義(P<0.05)。結(jié)論膜突蛋白高表達(dá)與乳腺癌轉(zhuǎn)移潛能增強(qiáng)呈正相關(guān),可能通過(guò)影響MTDH和nm-23表
3、達(dá)、增強(qiáng)上皮間質(zhì)轉(zhuǎn)化、增加MMP一9分泌等來(lái)增強(qiáng)乳腺癌細(xì)胞的侵襲轉(zhuǎn)移能力?!娟P(guān)鍵詞】乳腺癌;腫瘤轉(zhuǎn)移;膜突蛋白;侵襲;轉(zhuǎn)移【中圖分類(lèi)號(hào)】R73—37【文獻(xiàn)標(biāo)志碼】Adoi:10.3969/i.issn.1672—8467.2013.06.009RelationshipbetweenmoesinexpressionandbreastcancermetastasisNIXiang,SHAOZhi—mink(DepartmentofBreastSurgery,ShanghaiCancerCenter,F(xiàn)udanUniversity,Shanghai200032,C
4、hina)[Abstract]ObjectiveToexploretheinternalrelationshipbetweenmoesinexpressionandbreastcancermetastasis.MethodsImmunohistochemistry(IHC),RT_PCRandWesternblotwere"usedtoidentifymoesinexpressioninbreastcancertissuesamplesandaseriesofhumanbreastcancercel1lineswithdifferentmetastaticp
5、otentials.RNAitechniquecombinedwithinvasionandmotilityassayinvitrowerealsousedtorevealtheinterrelationshipbetweenmoesindeficiencyandinvasionandmotilityabilityofbreastcancercells.ResultsIHCanalysisshowedthatmoesinweremainlydistributed0nthecellmembraneandcytoplasm.Itsexpressionwashig
6、herinmetastaticbreastcancertissuesamplesthaninnon-metastaticones(P0.001,y。=17.536).Westernblotresultsrevealedpositivecorrelationbetweenmoesinexpressionandmetastaticpotentialofbreastcancercells.TheresultsofTranswellexperimentdisplayedthatmoesinexpressionsilencingremarkablyinhibitedi
7、nvasionandmotilityabilityofbreastcancercells,especiallythecellswithhighmetastaticpotentia1.Aftermoesinexpression,thelevelsofMTDHmRNAandnm-23mRNAinbreastcancercells(P<0.05)significantlydecreased,whilevimentinexpressionincreased,andtheexpressionsofBcadherinandMMP-9decreased.Conclusio
8、nsMoesinover—expressionpre