p14ARF基因在大肠癌中的表达及意义
刘辉, 罗丽明, 倪国文, 李华, 郭建国, 武汉市普仁医院消化内科 湖北省武汉市 430081
周中银, 武汉大学人民医院消化内科 湖北省武汉市 430060
通讯作者: 刘辉, 430081, 湖北省武汉市青山区红卫路本溪街1号, 武汉市普仁医院消化内科. whzzy@tom.com
电话: 027-68868236
收稿日期: 2005-03-18 接受日期: 2005-04-13
摘要
目的: 探讨p14ARF基因在大肠癌中的表达及其生物学意义.
, 百拇医药
方法: 应用免疫组织化学(S-P)法和TdT介导的dUTP缺口末端标记技术原位观察60例大肠癌患者的癌组织、癌旁组织和正常组织中p14ARF基因蛋白的表达和细胞凋亡.
结果: 癌组织p14ARF基因的阳性表达相对含量(PU)(9.57±1.03)明显低于癌旁(28.17±5.26，t = 2.51，P = 0.02<0.05)和正常组织(43.76±7.14，t = 3.61，P = 0.006<0.01);癌旁凋亡指数(AI)(8.51±2.63%)高于癌组织凋亡指数(AI)(5.65±1.76%，t = 2.18，P = 0.04<0.05);p14ARF基因蛋白的阳性表达按患者的性别、年龄、肿瘤大小分组比较各组间无明显区别;按癌组织的分化程度、淋巴结转移和Dukes分期比较，低分化组、有淋巴结转移组和Dukes C+D期组的p14ARF基因蛋白表达分别低于高分化组(7.93±1.89 vs 12.76±2.28，t = 2.36，P = 0.03<0.05)、无淋巴结转移组(7.21±1.95 vs 13.12±2.33，t = 2.34，P = 0.03<0.05)和Dukes A+B期组(7.87±1.18 vs 12.03±2.15，t = 2.36，P = 0.03<0.05).
, 百拇医药
结论: p14ARF基因在大肠癌组织中表达下调，从而抑制大肠癌的细胞凋亡，这可能是大肠癌发生、发展的机制之一;p14ARF基因的表达下调与大肠癌的恶性生物学行为有关.
刘辉, 罗丽明, 倪国文, 李华, 郭建国, 周中银. p14ARF基因在大肠癌中的表达及意义. 世界华人消化杂志 2005;13(13):1597-1599
Serrano M, Hannon GJ, Beach D. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4.
Nature 1993;366:704-707
2 Larsen CJ. pRB, p53, p16INK4a, senescence and malignant transformation. Bull Cancer 2004;91:399-402
, 百拇医药
3 陈世耀, 吴同法, 刘厚钰, 王吉耀, 张善身, 张希德. 10 a内镜检查分析. 世界华人消化杂志 1999;7:15-17
4 Wang Z, Wang F, Wang WQ, Gao Q, Wei WL, Yang Y, Wang GY. Correlation of N-myc downstream-regulated
gene 1 overexpression with progressive growth of colorectal neoplasm. World J Gastroenterol 2004;10:550-554
5 宋今丹, 高丰,蒋英丽,赵欣, 陈誉华,王芸庆.细胞凋亡与大肠肿瘤.世界华人消化杂志 2002;10:429-431
6 申洪. 免疫组织化学染色定量方法的研究(Ⅲ). 中国组织化学与细胞化学杂志 1995;4:89-92
, 百拇医药
7 Qiao D, Gaitonde SV, Qi W, Martinez JD. Deoxycholic acid suppressesp53 by stimulating proteasome-mediated p53
protein degradation. Carcinogenesis 2001;22:957-964
8 Calabro V, Mansueto G, Santoro R, Gentilella A, Pollice A, GhioniP, Guerrini L, La Mantia G. Inhibition of p63 transcriptional
activity by p14ARF: functional andphysical link between human ARF tumor suppressor and a member of thep53
, 百拇医药
family. Mol Cell Biol 2004;24:8529-8540
9 Ito T, Nishida N, Fukuda Y, Nishimura T, Komeda T, Nakao K.Alteration of the p14 (ARF) gene and p53 status in
human hepatocellular carcinomas. JGastroenterol 2004;39:355-361
10 Xiao EH, Li JQ, Huang JF. Effects of P53 on apoptosis andproliferation of hepatocellular carcinoma cells treated with
transcatheter arterialchemoembolization. World J Gastroenterol 2004;10:190-194
, 百拇医药
11 Martinez JC, Palomino JC, Cabello A, Sepulveda JM, de la Camara AG,Ricoy JR. HDM2 overexpression and focal loss of
p14/ARF expression mayderegulate the P53 tumour suppressor pathway in meningealhaemangiopericytomas.
Histopathology 2005;46:184-194
12 Wang YC, Lin RK, Tan YH, Chen JT, Chen CY, Wang YC. Wild-type P53overexpression and its correlation with MDM2
, 百拇医药
and p14ARF alterations: analternative pathway to non-small-cell lung cancer. J Clin Oncol 2005;23:154-164
13 Herman JG, Merlo A, Mao L, Lapidus RG, Issa JP, Davidson NE,Sidransky D, Baylin SB. Inactivation of the
CDKN2/P16/MTS1 gene is frequentlyassociated with aberrant DNA methylation in all common humancancers.
Cancer Res 1995;55:4525-4530
14 Esteller M, Tortola S, Toyota M, Capella G, Peinado MA, Baylin SB,Herman JG. Hypermethylation-associated
, http://www.100md.com
inactivation of p14 (ARF) isindependent of P16 (INK4a) methylation and p53 mutational status. CancerRes
2000;60:129-133
15 Sarbia M, Geddert H, Klump B, Kiel S, Iskender E, Gabbert HE.Hypermethylation of tumor suppressor genes (p16INK4A,p14ARF and APC) inadenocarcinomas of the upper gastrointestinal tract. Int J Cancer 2004;111:224-228
16 Radfar A, Unnikrishnan I, Lee HW, DePinho RA, Rosenberg N. p19 (Arf)induces p53-dependent apoptosis during
abelson virus-mediated pre-Bcell transformation. Proc Natl Acad Sci USA 1998;95:13194-13199
编辑 张海宁, 百拇医药( 刘 辉,罗丽明, 倪国文, 李 华, 郭建国,周中银)
周中银, 武汉大学人民医院消化内科 湖北省武汉市 430060
通讯作者: 刘辉, 430081, 湖北省武汉市青山区红卫路本溪街1号, 武汉市普仁医院消化内科. whzzy@tom.com
电话: 027-68868236
收稿日期: 2005-03-18 接受日期: 2005-04-13
摘要
目的: 探讨p14ARF基因在大肠癌中的表达及其生物学意义.
, 百拇医药
方法: 应用免疫组织化学(S-P)法和TdT介导的dUTP缺口末端标记技术原位观察60例大肠癌患者的癌组织、癌旁组织和正常组织中p14ARF基因蛋白的表达和细胞凋亡.
结果: 癌组织p14ARF基因的阳性表达相对含量(PU)(9.57±1.03)明显低于癌旁(28.17±5.26，t = 2.51，P = 0.02<0.05)和正常组织(43.76±7.14，t = 3.61，P = 0.006<0.01);癌旁凋亡指数(AI)(8.51±2.63%)高于癌组织凋亡指数(AI)(5.65±1.76%，t = 2.18，P = 0.04<0.05);p14ARF基因蛋白的阳性表达按患者的性别、年龄、肿瘤大小分组比较各组间无明显区别;按癌组织的分化程度、淋巴结转移和Dukes分期比较，低分化组、有淋巴结转移组和Dukes C+D期组的p14ARF基因蛋白表达分别低于高分化组(7.93±1.89 vs 12.76±2.28，t = 2.36，P = 0.03<0.05)、无淋巴结转移组(7.21±1.95 vs 13.12±2.33，t = 2.34，P = 0.03<0.05)和Dukes A+B期组(7.87±1.18 vs 12.03±2.15，t = 2.36，P = 0.03<0.05).
, 百拇医药
结论: p14ARF基因在大肠癌组织中表达下调，从而抑制大肠癌的细胞凋亡，这可能是大肠癌发生、发展的机制之一;p14ARF基因的表达下调与大肠癌的恶性生物学行为有关.
刘辉, 罗丽明, 倪国文, 李华, 郭建国, 周中银. p14ARF基因在大肠癌中的表达及意义. 世界华人消化杂志 2005;13(13):1597-1599
Serrano M, Hannon GJ, Beach D. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4.
Nature 1993;366:704-707
2 Larsen CJ. pRB, p53, p16INK4a, senescence and malignant transformation. Bull Cancer 2004;91:399-402
, 百拇医药
3 陈世耀, 吴同法, 刘厚钰, 王吉耀, 张善身, 张希德. 10 a内镜检查分析. 世界华人消化杂志 1999;7:15-17
4 Wang Z, Wang F, Wang WQ, Gao Q, Wei WL, Yang Y, Wang GY. Correlation of N-myc downstream-regulated
gene 1 overexpression with progressive growth of colorectal neoplasm. World J Gastroenterol 2004;10:550-554
5 宋今丹, 高丰,蒋英丽,赵欣, 陈誉华,王芸庆.细胞凋亡与大肠肿瘤.世界华人消化杂志 2002;10:429-431
6 申洪. 免疫组织化学染色定量方法的研究(Ⅲ). 中国组织化学与细胞化学杂志 1995;4:89-92
, 百拇医药
7 Qiao D, Gaitonde SV, Qi W, Martinez JD. Deoxycholic acid suppressesp53 by stimulating proteasome-mediated p53
protein degradation. Carcinogenesis 2001;22:957-964
8 Calabro V, Mansueto G, Santoro R, Gentilella A, Pollice A, GhioniP, Guerrini L, La Mantia G. Inhibition of p63 transcriptional
activity by p14ARF: functional andphysical link between human ARF tumor suppressor and a member of thep53
, 百拇医药
family. Mol Cell Biol 2004;24:8529-8540
9 Ito T, Nishida N, Fukuda Y, Nishimura T, Komeda T, Nakao K.Alteration of the p14 (ARF) gene and p53 status in
human hepatocellular carcinomas. JGastroenterol 2004;39:355-361
10 Xiao EH, Li JQ, Huang JF. Effects of P53 on apoptosis andproliferation of hepatocellular carcinoma cells treated with
transcatheter arterialchemoembolization. World J Gastroenterol 2004;10:190-194
, 百拇医药
11 Martinez JC, Palomino JC, Cabello A, Sepulveda JM, de la Camara AG,Ricoy JR. HDM2 overexpression and focal loss of
p14/ARF expression mayderegulate the P53 tumour suppressor pathway in meningealhaemangiopericytomas.
Histopathology 2005;46:184-194
12 Wang YC, Lin RK, Tan YH, Chen JT, Chen CY, Wang YC. Wild-type P53overexpression and its correlation with MDM2
, 百拇医药
and p14ARF alterations: analternative pathway to non-small-cell lung cancer. J Clin Oncol 2005;23:154-164
13 Herman JG, Merlo A, Mao L, Lapidus RG, Issa JP, Davidson NE,Sidransky D, Baylin SB. Inactivation of the
CDKN2/P16/MTS1 gene is frequentlyassociated with aberrant DNA methylation in all common humancancers.
Cancer Res 1995;55:4525-4530
14 Esteller M, Tortola S, Toyota M, Capella G, Peinado MA, Baylin SB,Herman JG. Hypermethylation-associated
, http://www.100md.com
inactivation of p14 (ARF) isindependent of P16 (INK4a) methylation and p53 mutational status. CancerRes
2000;60:129-133
15 Sarbia M, Geddert H, Klump B, Kiel S, Iskender E, Gabbert HE.Hypermethylation of tumor suppressor genes (p16INK4A,p14ARF and APC) inadenocarcinomas of the upper gastrointestinal tract. Int J Cancer 2004;111:224-228
16 Radfar A, Unnikrishnan I, Lee HW, DePinho RA, Rosenberg N. p19 (Arf)induces p53-dependent apoptosis during
abelson virus-mediated pre-Bcell transformation. Proc Natl Acad Sci USA 1998;95:13194-13199
编辑 张海宁, 百拇医药( 刘 辉,罗丽明, 倪国文, 李 华, 郭建国,周中银)
