p73和p51在腫瘤發生及動物發育中扮演的角色

中山醫學大學機構典藏 CSMUIR > 醫學科技學院 > 生物醫學科學學系暨碩士班 > 研究計劃 > Item 310902500/2716

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/2716

Title:	p73和p51在腫瘤發生及動物發育中扮演的角色 Roles of p73 and p51 in Tumorigenesis and Animal Development
Authors:	潘惠錦 Pan, Hui-Chin
Contributors:	中山醫學院生命科學系
Keywords:	對偶基因表現分析;基因突變;肝細胞癌;p73基因;腫瘤抑制基因;腫瘤發生;發育 Allelic expression；Gene mutation；Hepatocellular carcinoma (HCC)；p73 gene；Tumor suppressor gene；Tumorigenesis；Development
Date:	2000
Issue Date:	2010-11-05T10:49:03Z (UTC)
Abstract:	在過半的人類癌症中皆發現有抑癌基因p53的突變。近來發現一個新的p53相似物，稱為p73，它具有與p53的DNA結合、轉活化及寡聚物聚合部位非常高度的序例相似性。研究顯示p73具有與p53相似的寡聚合及轉活化能力，並且p73可活化p53-感應基因如p21，並可經由引發細胞凋亡來抑制細胞生長。為探討p73是否與肝細胞癌的病因有關，我們檢查了18對正常及肝癌組織在p73基因的基因座缺失、基因座不平衡表達、以及基因突變等情況。PCR-RFLP分析其exon 2的多形性顯示，在15個正常檢體中有5個是異形合子，而其中沒有任何一個在相對的癌組織中有缺失。檢查RNA的樣本顯示兩個基因座的RNA皆存在於5個異形合子，顯示p73基因在肝組織是雙基因座表達。有趣的是，p73基因表達的量在癌組織中總是比在相對的正常組織中高。最後，單股構形多形性及定序分析顯示在外顯子6、9、14有數個多形性及在內顯子6、9也有一些變異。但是在整個p73的編碼區域並沒有任何的突變。這些結果指出p73並不像p53一樣在癌腫中扮演抑癌的角色，反而大量的表達p73基因可能與肝癌的病因有關。 Mutations in the p53 tumor suppressor gene have been found in about half of all human cancers. Recently, a novel gene encoding a protein, termed p73, was identified with remarkable sequence similarity to the DNA-binding, transactivation, and oligomerization domains of p53. It was shown that p73 possess oligomerization and transactivation properties similar to p53 and it could activate p53-responsive genes such as p21, and suppress cell growth by inducing apoptosis. To investigate whether p73 is involved in the pathogenesis of hepatocellular carcinoma, we examined the presence of allelic loss, allelic expression imbalance and mutations of p73 gene in 18 pairs of normal and hepatocellular cancer tissues. PCR-RFLP analysis of a polymorphism in exon 2 revealed that 5 out of 15 normal samples were heterozygous and none of them were lost in the cancer counterparts. Both alleles were present in RNA samples from the five heterozygous individuals, indicating that p73 was biallelically expressed in the liver tissue. Interestingly, the expression level of p73 was consistently high in the cancerous tissues, in contrast to very low expression in the paired normal tissues. Finally, single strand conformation polymorphism and sequencing analysis revealed several polymorphisms in exon 6, 9, 14, as well as some variations in intron 6 and 9, but no mutations were found in the coding sequence of the p73 gene. These results indicate that p73 does not play a role in suppressing tumor growth as p53 does, but overexpression of p73 may somehow contribute to the pathogenesis of hepatocellular carcinoma.
URI:	https://ir.csmu.edu.tw:8080/handle/310902500/2716
Appears in Collections:	[生物醫學科學學系暨碩士班] 研究計劃

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