轉(zhuǎn)錄因子GATA4在小鼠肝臟發(fā)育和肝癌發(fā)生中的作用及相關(guān)機(jī)制探討.pdf

1、第二軍醫(yī)大學(xué)博士學(xué)位論文轉(zhuǎn)錄因子GATA4在小鼠肝臟發(fā)育和肝癌發(fā)生中的作用及相關(guān)機(jī)制探討姓名：任傳路申請學(xué)位級別：博士專業(yè)：人體解剖與組織胚胎學(xué)指導(dǎo)教師：劉厚奇20050401中文摘要GATA4參與肝發(fā)育，是否在肝癌中高表達(dá)未見報(bào)道。我們旨從胎肝、肝癌組織芯片和細(xì)胞株水平檢測GATA4的表達(dá)并探討其與肝細(xì)胞分化的關(guān)系。發(fā)現(xiàn)其在胎肝、肝癌組織或細(xì)胞中高表達(dá)，與分化程度負(fù)相關(guān)且較AFP更敏感。將其轉(zhuǎn)染小鼠正常肝細(xì)胞后促進(jìn)細(xì)胞增殖并上調(diào)AFP

2、的表達(dá)，同時(shí)上調(diào)PCNA和凋亡抑制基因Bcl一2及BclXL，并下調(diào)Ecadherin。阿霉素作用肝癌細(xì)胞后，隨著GATA4遞減，凋亡細(xì)胞漸增，AFP、Bcl2和BclXL的表達(dá)漸低，但均稍滯后于GATA4。提示GA]隊(duì)4可能通過上調(diào)AFP、降低細(xì)胞粘附及抑制細(xì)胞凋亡促進(jìn)肝癌發(fā)生。AbstractTranscriptionalfactorGATA4israrelyreportedtobeexpressedinheaptocarcinom

3、athoughitisindispensableinliverdevelopmentWeaimedtodetectGATA4expressioninfetalliver，heaptocarcinomatissuechipsandcelllinesandexploreitsrelationshipwithbepatocyledifferentiationWefoundthatGATA4washighlyexpressedinfetalli

4、vertissuechipsandcelllinesofheaptocarcinomaandWaSnegativelycorrelatedwithhepatocytedifferentiationandmoresensiWethanAFPinheaptocarcinomatissuechipsAftertransfectedintonormallivercelllinesGATA4wasfoundtOpromotecellprolife

5、ration，up—regulatePCNA，apoptosisinhibitinggeneBcl2andBclXLanddown—regulateE—cadhennWitllthedecrementofGATA4afteruseofdoxorubicineinlivecancercelllines，theincreasingapoptoticceilsandthedecliningexpressionofAFP、Bcl一2andBcl