【文章內(nèi)容簡介】 cadherin基因本身并未發(fā)生缺失突變（12）。Yu（2002）進(jìn)一步研究顯示Tcadherin基因啟動子在肝癌中高度甲基化，而Ecadherin基因啟動子在肝癌中不發(fā)生甲基化，表明在Cadherin細(xì)胞粘附分子超家族中Tcadherin基因啟動子甲基化在肝癌中具有高度特異性,且Tcadherin基因啟動子甲基化與Tcadherin基因失活密切相關(guān)（26）這些。研究表明Tcadherin基因啟動子甲基化是Tcadherin基因在肝癌中失活的主要機(jī)制。Takeuchi在對皮膚鱗癌細(xì)胞株的研究中發(fā)現(xiàn)，與2ug/ml去甲基化藥物5aza2’deoxycytidine共孵6天能使皮膚鱗癌細(xì)胞株恢復(fù)Tcadherin分子表達(dá)（17）。但目前對Tcadherin基因失活與肝癌惡性分化程度、肝內(nèi)轉(zhuǎn)移及復(fù)發(fā)等惡性生物學(xué)特征的關(guān)系，以及應(yīng)用去甲基化藥物是否能誘導(dǎo)Tcadherin分子在肝癌細(xì)胞株中重新表達(dá)，并抑制肝癌細(xì)胞的增殖、侵襲及轉(zhuǎn)移等惡性特征全世界尚無研究報道。本研究將進(jìn)一步研究Tcadherin在肝癌中的基因功能，調(diào)查缺失表達(dá)Tcadherin的肝癌細(xì)胞株重新表達(dá)Tcadherin是否能抑制肝癌細(xì)胞的增殖、侵襲及轉(zhuǎn)移等惡性生物學(xué)特征，并在裸鼠肝癌模型上加以證實。同時，進(jìn)一步研究其基因功能的分子機(jī)制。在臨床切除的肝癌標(biāo)本中研究Tcadherin基因失活與肝癌惡性分化程度、轉(zhuǎn)移及復(fù)發(fā)等惡性生物學(xué)特征的關(guān)系，進(jìn)一步揭示Tcadherin基因失活與臨床肝癌預(yù)后的關(guān)系。在肝癌細(xì)胞株及裸鼠肝癌模型上證實是否去甲基化藥物能重新誘導(dǎo)Tcadherin分子表達(dá)，并抑制肝癌細(xì)胞的增殖、侵襲及轉(zhuǎn)移等惡性生物學(xué)特征，觀察其潛在的治療作用和可能的毒副作用。由于國內(nèi)外尚無類似研究報道，申請人具有研究Tcadherin基因與C6細(xì)胞惡性生物學(xué)特征的關(guān)系及其分子機(jī)制的豐富經(jīng)驗，預(yù)期該研究成果能達(dá)國際先進(jìn)水平。主要參考文獻(xiàn)： 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