CCND1、CDK5R2、PTP4A1、CDK4及THY1基因在肝細胞癌之異常表現探討

Abnormal expression of CCND1，CDK5R2，PTP4A1，CDK4 and THY1 genes in hepatocellular carcinoma

盧正偉(Jeng-Wei Lu)

指導教授 ： 胡若梅 ； 張建國

亞洲大學/資訊學院/生物資訊學系碩士班/碩士(2006年)

摘要

異常的啟動子區域甲基化作用常於腫瘤抑制基因出現並且會抑制其基因表現此現象可能與腫瘤形成具有關聯。我們針對肝細胞癌進行研究以下這些腫瘤相關基因CCND1、CDK5R2、PTP4A1、THY1、CDK4，並且探討其對於甲基化作用和臨床之關聯性。為了要瞭解CCND1、CDK5R2、PTP4A1、THY1、CDK4基因在人類肝細胞癌之表現情況，我們利用即時定量聚合酶反應作用與免疫組織化學染色分析64位肝細胞癌患者之癌組織和非癌組織。這個實驗結果顯示，CCND1、CDK5R2、PTP4A1、THY1在大部份的癌組織中基因表現量普遍降低，CDK4基因則是在於癌組織中基因表現量有普遍增加之情況，在甲基化作用的分析之中THY1、PTP4A1、CDK5R2基因在啟動子區域有甲基化情況產生，CCND1、CDK4基因在啟動子區域則完全無甲基化情況出現。所以我們確定了THY1、PTP4A1、CDK5R2基因表現量降低是因為DNA甲基化所造成。至於CCND1基因在癌組織中表現量降低及CDK4基因在癌組織中表現量增加之作用機制我們並不瞭解，需要進一步深入探討。

關鍵字

肝細胞癌 ； 甲基化 ； 基因表現

並列摘要

Aberrant promoter methylation of CpG islands of tumor suppressor genes inhibits expression of the genes and may lead to tumorigenesis. We investigated the methylation profile of tumor associated genes CCND1, CDK5R2, PTP4A1,THY1 and CDK4 in hepatocellular carcinoma（HCC）and correlated the data with clinical findings. In order to understand the expression of CCND1, CDK5R2, PTP4A1, CDK4 and THY1 in human hepatocellular carcinoma. we examined 64 HCCs and their paired non-cancerous tissues by real-time quantitative reverse transcription-polymerase chain reaction and immunohistochemical analysis. The results showed that CCND1, CDK5R2, PTP4A1 and THY1 were underexpressed, while CDK4 was upregulated in most of the cancerous tissues. Methylation analysis of CpG sites at the promoter areas showed that THY1, PTP4A1 and CDK5R2 were methylated while CCND1 and CDK4 were not, thus confirming that the underexpression of THY1, PTP4A1 and CDK5R2 was due to aberrant DNA methylation. The mechanism of CCND1’s down regulation and CDK4’s upregulation in cancerous tissue need to be further studied

並列關鍵字

Hepatocellular carcinoma ； Methylation ； Gene expression expression

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