散发性结直肠癌中P33～（ING1b）的表达、突变及甲基化研究
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摘要
目的：
ING1(inhibitor of growth 1)基因是新近发现的抑癌基因，它的表达可抑制细胞生长、参与细胞衰老调节和诱导细胞凋亡。研究发现ING1基因有三种不同的亚型p33~(ING1b)、p47~(ING1a)和p24~(ING1c)。目前对P33~(ING1b)的研究较多，它是野生型p53的分子“伴侣”。在人体某些肿瘤中，P33~(ING1b) mRNA的表达水平降低，而基因突变较少，提示p33~(ING1b)并非通过突变而是通过低水平表达影响肿瘤的发生发展。在结直肠癌中，EphA7、E2F等基因的低表达是因为其启动子的甲基化引起的。迄今为止，p33~(ING1b)在结直肠癌中的研究报道较少，尚未见p33~(ING1b)启动子甲基化的研究报道。本研究检测散发性结直肠癌中p33~(ING1b)的mRNA表达、基因突变和启动子甲基化的情况，旨在探讨p33~(ING1b)基因在散发性结直肠癌发生发展中的作用和意义。
方法：
P33~(INC1b) mRNA表达、基因突变和启动子甲基化分别用半定量逆转录-聚合酶链式反应(reverse transcription-polymerase chain reaction，RT-PCR)、聚合酶链式反应-单链构像多态性(PCR-single strain conformation polymorphism，PCR-SSCP)和甲基化特异性PCR(Methylation Specific PCR，MSP)进行分析。
结果：
1、在46例结直肠癌组织和相应的正常粘膜组织中，p33~(ING1b) mRNA都有不同程度的表达，p33~(ING1b) mRNA在癌组织和正常粘膜组织中的平均光密度比值分别为0.52和1.28，有显著的统计学差异(P＜0.05)。Dukes C/D期癌组织中p33~(ING1b) mRNA的平均光密度比值为0.38，低于Dukes A/B期的0.65，有显著的统计学差异(P＜0.05)。但它们在不同年龄、性别、肿瘤部位、癌肿侵犯肠管范围和肿瘤分化程度组的比较无明显差别(P＞0.05)。
2、对p33~(ING1b)基因外显子1和外显子2的编码区进行检测，46例结直
Purpose:
ING1 has been identified as a novel tumor suppressor gene, and proved to be involved in the modulation of cell cycle. Its expression can inhibit cell growth, control celluar aging, and induce cell apotosis. It has more than 3 different splices at transcription, and becomes three subtypes (p33~(ING1b)、 p47~(ING1a) 和 p24~(ING1c)) at least. P33~(ING1b) is a 'molecular partner' of wild type p53. Decreased expression of p33~(ING1b) mRNA has been found in some human tumors, but mutation of p33~(ING1b) was rarely found. It suggests that p33~(ING1b) exploits the effect on the genesis and progression of cancer by decreased expression, not by mutation. Decreased expression of EphA7、 CDX2、 E2F are caused by their promoter methylaion in colorectal cancer. There are seldom reports about p33~(ING1b) in colorectal cancer, and no report about its methylaion by now. Our study was to explore the effect and siginificance of p33~(ING1b) on the genesis and progression of sporadic colorectal cancer by detecting mRNA expression, mutation and promoter methylaion of p33~(ING1b).
Methods:
mRNA expression, mutation and promoter methylaion of p33~(ING1b) in 46 specimens of sporadic colorectal cancerous tissues and matched normal tissues were detected by semi-quantitative RT-PCR, PCR-SSCP and MSP, respectively.
Results:
(1) All 46 samples of tumor tissues and matched normal mucosae tissues express p33~(ING1b) mRNA. The average ratios of light density of P33~(ING1b) mRNA in the cancerous and normal tissues were 0.52 and 1.28, significant difference between
ING1(inhibitor of growth 1)基因是新近发现的抑癌基因，它的表达可抑制细胞生长、参与细胞衰老调节和诱导细胞凋亡。研究发现ING1基因有三种不同的亚型p33~(ING1b)、p47~(ING1a)和p24~(ING1c)。目前对P33~(ING1b)的研究较多，它是野生型p53的分子“伴侣”。在人体某些肿瘤中，P33~(ING1b) mRNA的表达水平降低，而基因突变较少，提示p33~(ING1b)并非通过突变而是通过低水平表达影响肿瘤的发生发展。在结直肠癌中，EphA7、E2F等基因的低表达是因为其启动子的甲基化引起的。迄今为止，p33~(ING1b)在结直肠癌中的研究报道较少，尚未见p33~(ING1b)启动子甲基化的研究报道。本研究检测散发性结直肠癌中p33~(ING1b)的mRNA表达、基因突变和启动子甲基化的情况，旨在探讨p33~(ING1b)基因在散发性结直肠癌发生发展中的作用和意义。
方法：
P33~(INC1b) mRNA表达、基因突变和启动子甲基化分别用半定量逆转录-聚合酶链式反应(reverse transcription-polymerase chain reaction，RT-PCR)、聚合酶链式反应-单链构像多态性(PCR-single strain conformation polymorphism，PCR-SSCP)和甲基化特异性PCR(Methylation Specific PCR，MSP)进行分析。
结果：
1、在46例结直肠癌组织和相应的正常粘膜组织中，p33~(ING1b) mRNA都有不同程度的表达，p33~(ING1b) mRNA在癌组织和正常粘膜组织中的平均光密度比值分别为0.52和1.28，有显著的统计学差异(P＜0.05)。Dukes C/D期癌组织中p33~(ING1b) mRNA的平均光密度比值为0.38，低于Dukes A/B期的0.65，有显著的统计学差异(P＜0.05)。但它们在不同年龄、性别、肿瘤部位、癌肿侵犯肠管范围和肿瘤分化程度组的比较无明显差别(P＞0.05)。
2、对p33~(ING1b)基因外显子1和外显子2的编码区进行检测，46例结直
Purpose:
ING1 has been identified as a novel tumor suppressor gene, and proved to be involved in the modulation of cell cycle. Its expression can inhibit cell growth, control celluar aging, and induce cell apotosis. It has more than 3 different splices at transcription, and becomes three subtypes (p33~(ING1b)、 p47~(ING1a) 和 p24~(ING1c)) at least. P33~(ING1b) is a 'molecular partner' of wild type p53. Decreased expression of p33~(ING1b) mRNA has been found in some human tumors, but mutation of p33~(ING1b) was rarely found. It suggests that p33~(ING1b) exploits the effect on the genesis and progression of cancer by decreased expression, not by mutation. Decreased expression of EphA7、 CDX2、 E2F are caused by their promoter methylaion in colorectal cancer. There are seldom reports about p33~(ING1b) in colorectal cancer, and no report about its methylaion by now. Our study was to explore the effect and siginificance of p33~(ING1b) on the genesis and progression of sporadic colorectal cancer by detecting mRNA expression, mutation and promoter methylaion of p33~(ING1b).
Methods:
mRNA expression, mutation and promoter methylaion of p33~(ING1b) in 46 specimens of sporadic colorectal cancerous tissues and matched normal tissues were detected by semi-quantitative RT-PCR, PCR-SSCP and MSP, respectively.
Results:
(1) All 46 samples of tumor tissues and matched normal mucosae tissues express p33~(ING1b) mRNA. The average ratios of light density of P33~(ING1b) mRNA in the cancerous and normal tissues were 0.52 and 1.28, significant difference between
引文
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1. Hung KE, Chung DC.Colorectal cancer screening: today and tomorrow. South Med J. 2006;99:240-246
2．李连弟、饶克勤、张思维、等．中国12市县1993年．1997年肿瘤发病和死亡登记资料统计分析．中国肿瘤 2002：11：497-507．
3. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990;61:759-767.
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5. Issa JP: The epigenetics of colorectal cancer. Ann NY Acad Sci. 2000; 910: 140-153.
6. Sanz-Casla MT, Maestro ML, Vidaurreta M, et al. p16 Gene methylation in colorectal tumors: correlation with clinicopathological features and prognostic value.Dig Dis;23:151-155.
7. Shen L, Kondo Y, Hamilton SR, et al. P14 methylation in human colon cancer is associated with microsatellite instability and wild-type p53. Gastroenterology. 2003; 124:626-633.
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