[散发性结直肠癌中肿瘤抑制基因ING1的突变、杂合性缺失及表达]

[Mutation, loss of heterozygosity, and expression of tumor suppressor gene ING1 in sporadic colorectal carcinoma].

作者信息

Wei Jian-Bao, Chen Li-Sheng, Gao Feng

机构信息

Department of Coloproctological Surgery, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, 530021, P. R. China.

出版信息

Ai Zheng. 2005 Feb;24(2):141-4.

DOI:

PMID:15694021

Abstract

BACKGROUND & OBJECTIVE: Inhibitor of growth 1 (ING(1)) gene has been identified as a novel tumor suppressor gene. Its over-expression can inhibit cell growth, and induce cell apoptosis. This study was to explore the effect and significance of ING(1) gene in occurrence and progression of sporadic colorectal cancer.

METHODS

The expression, mutation, and loss of heterozygosity (LOH) of ING(1) gene in 46 specimens of sporadic colorectal cancer tissues and adjuvant normal mucous membrane tissues were detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), PCR-single strain conformation polymorphism (PCR-SSCP), and microsatellite markers, respectively.

RESULTS

(1)The average ratios of light density of p33/ING(1) mRNA, and p47/ING(1) mRNA in the cancerous tissues were significantly lower than those in normal tissues (0.52 vs. 1.28, P < 0.01; 0.51 vs. 1.21, P < 0.01). Difference between the 2 mRNA splices was not significant in the matched tissues (P > 0.05). (2) The average ratios of light density of p33/ING(1) mRNA, and p47/ING(1) mRNA in the cancerous tissues of Dukes' C, D stage were significantly lower than those in cancerous tissues of Dukes' A, B stage (0.38 vs. 0.65, P < 0.01; 0.40 vs. 0.63, P < 0.01). (3) Of the 46 cases, no mutation of ING(1) gene was detected, only 5 (10.9%)cases of LOH were found.

CONCLUSIONS

Abnormal alteration of ING(1) gene is rare in sporadic colorectal cancer. Its down-regulation may happen in transcription or post-transcription, and correlates tightly with the occurrence and progression of sporadic colorectal cancer.

摘要

背景与目的

生长抑制因子1（ING(1)）基因已被确认为一种新型肿瘤抑制基因。其过表达可抑制细胞生长并诱导细胞凋亡。本研究旨在探讨ING(1)基因在散发性结直肠癌发生发展中的作用及意义。

方法

分别采用半定量逆转录-聚合酶链反应（RT-PCR）、聚合酶链反应-单链构象多态性（PCR-SSCP）及微卫星标记检测46例散发性结直肠癌组织及癌旁正常黏膜组织中ING(1)基因的表达、突变及杂合性缺失（LOH）情况。

结果

（1）癌组织中p33/ING(1) mRNA和p47/ING(1) mRNA的平均光密度比值显著低于正常组织（0.52对1.28，P<0.01；0.51对1.21，P<0.01）。在配对组织中，两种mRNA剪接体之间的差异无统计学意义（P>0.05）。（2）Dukes' C、D期癌组织中p33/ING(1) mRNA和p47/ING(1) mRNA的平均光密度比值显著低于Dukes' A、B期癌组织（0.38对0.65，P<0.01；0.40对0.63，P<0.01）。（3）46例病例中，未检测到ING(1)基因的突变，仅发现5例（10.9%）存在LOH。