期刊文献+

胰腺癌中p16基因甲基化改变及其蛋白表达分析 被引量:6

p16 gene methylation and its protein expression in pancreatic carcinoma
暂未订购
导出
摘要 目的探讨胰腺癌与癌旁组织中p16基因启动子区异常甲基化的改变及其蛋白表达的特点,以及其与胰腺癌发生发展的关系。方法分别采用免疫组化SP法及甲基化特异PCR(MSP)检测46例人胰腺癌和癌旁组织中p16基因表达及其甲基化的水平,并结合临床资料进行分析。结果胰腺癌中p16蛋白表达率为41.3%(19/46),而癌旁组织表达率为95.7%(44/46),两者有差异显著性(P<0.01)。p16蛋白阳性的19例胰腺癌标本中均未检出基因甲基化;p16蛋白缺失的27例标本中有18例检出基因甲基化,甲基化率为39.1%。p16基因甲基化与蛋白缺失有明显关系(P<0.05)。p16基因表达及其启动子区甲基化的发生率与胰腺癌的大小,患者性别?年龄的差异无显著意义(P>0.05),但与组织分化程度?淋巴结转移?PTNM分期有显著意义(P<0.05)。结论p16基因启动子的异常甲基化可影响p16蛋白的表达,它们与胰腺癌的发生发展有关;p16甲基化和蛋白表达可能成为胰腺癌诊断及预后的候选标志物之一。 Objective To investigate aberrant methylation in the promoter area of p16 gene and p16 protein expression in human pancreatic carcinoma and in the corresponding tumor-adjacent tissues, and evaluate their role in the carcinogenesis and progression of tumor and its dinical significance. Methods Immunohistochemistry and MSP (methylation-specific PCR ) were performed on 46 samples of pancreatic carcinoma and their corresponding tumor-adjacent tissue specimens for p16 and its methylation. Results Expression rate of p16 protein was 41.3 % (19/46) in pancreatic carcinomas, 95.7 % (44/46) in corresponding tumor-adiucent tissues. Through MSP, the methylation rate in pancreatic carcinomas was 39. 1%. No gene methylation was found in 19 cases expressing p 1 6 protein, p 16 gene methylation was closely related to p 16 protein expression in pancreatic carcinoma ( P 〈 0.05 ). The expression of p16, the aberrant methylation in the promoter area of p 16 gene were no relationship with clinicopathological characteristics, such as tumor size, patient's sex and age (P 〉 0. 05 ); but were significantly related to the PTNM staging, histological differentiation, distant metastasis and lymph node metastasis ( P 〈 0.05 ). Conclusions Methylation in the promoter of p 16 gene and p 16 protein expression were associated with the development of pancreatic carcinoma and could be used as a putative prognostic indicator for malignancy.
出处 《中国普通外科杂志》 CAS CSCD 2007年第5期446-450,共5页 China Journal of General Surgery
关键词 胰腺肿瘤 P16基因 甲基化 甲基化特异性PCR P16蛋白表达 Pancreatic Neoplasms p 16 Gene Methylation Methylation-specific PCR p 16 Protein Expression
  • 相关文献

参考文献12

  • 1Yasui W,Yokozaki H,Fujimoto J,et al.Genetic and epigenetic alterations in multistep carcinogenesis of the stomach[J].Gastroenterol,2000,35(12):111-115.
  • 2Kamb A,Gruis NA,Wearer-Feldhaus J,et al.A cell cycle regulator potentially involved in genesis of many tumor types[J].Science,1994,264(5157):436-440.
  • 3东星,周卫东.胰腺癌的分子生物学研究进展[J].中国普通外科杂志,2004,13(6):454-456. 被引量:2
  • 4Jones PA,Laird PW.Cancer epigenetics comes of age[J].Nat Genet,1999,21(2):163-167.
  • 5Herman J G,Graff J R,Myohanen S,et al.Methylation-specific PCR:A novel PCR assay for methylation status of CpG island[J].Proc Natl Acad Sci USA,1996,93(18):9821-9826.
  • 6Ueki T,Toyota M,Sohn T,et al.Hypermethylation of multiple genes in pancreatic adenocarcinoma[J].Cancer Res,2000,60(7):1835-1839.
  • 7Sato N,Ueki T,Fukushima N,et al.Aberrant methylation of CpG islands in intraductal papillary muci-nous neoplasms of the pancreas[J].Gastroenterology,2002,123(1):365-372.
  • 8Naka T,Kabayashi M,Ashida K,et al.Aberrant p16INK4 expression related to clinical stage and prognosis in patients with pancreatic cancer[J].Int J Oncol,1998,12(5):1111-1116.
  • 9Hu Y X,Watanabe H,Ohtsubo K,et al.Frequent loss of p16 expression and its correlationwith clinicopathological parameters in pancreatic carcinorma[J].Ciln Cancer Res,1997,3(9):1473-1477.
  • 10Herman J G,Merlo A,Mao L,et al.Inactivation and CAKN/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human[J].Cancer Research,1995,55(20):4525.

二级参考文献22

  • 1Boring C ,Squires T,Tong T,et al.Cancer Statistics [ J ] .Cancer J Clin,1993,43(1) :7 -26.
  • 2Flanders TY,Foulkes WD.Pancreatic adenocarcinoma:epidemiology and genetics[ J].J Med Genet,1996,33(11) :889 -898.
  • 3Yanagisawa A,Ohtake K,Ohashi K,et al.Frequent C-ki-ras oncogene activation in mucous cell hyperplasias of pancreas suffering from chronic inflammation[ J].Cancer Res,1993,53(5) :953 -956.
  • 4Brigitte P,Sonke A,Ken B,et al.Analysis of K- ras mutation in pancreatic tissue after fine needle aspirates [ J ].Anticancer Res,1999,19(10) :2481 -2483.
  • 5Schwarte-Waldhoff I,Volpert OV,Bouck NP,et al.Snad4/DPC4-mediated tumor suppression through suppression of angiogenesis [ J ].Proc Natl Acad Sci USA,2000,97 (17) :9624 -9629.
  • 6Siard C,Kim S,Mirtosis C,et al.In testinal tumorigenesis in compound mutant mice of both DPC4 ( Smad4 ) and Apc genes[J].J Biol Chem,2000,275(7) :2063 -2072.
  • 7Yamada T,Nakamori S,Ohzato H.Detection of K-ras gene mutation in plasma DNA of patients with pancreatic adenocarcinoma:correlation with clinicopathological features [ J ] .Clin cancer Res,1998,4(6) :1527-1532.
  • 8Lley JR,Brown DM,Frasier MM,et al.The cancer associated Sm-like oncogene:a novel target for the gene therapy of pancreatic cancer [ J ].Surgery,2000,128(2) :353 -360.
  • 9Shichinohe T,Senmaru N,Furuuchi K,et al.Suppression of pancreatic cancer by the dominant negative mutant,N116Y [ J ].J Surg Res,1996,66(2) :125-130.
  • 10Bouvet M,Bold RI,Lee J,et al.Adenovirus-medioted wild type p53 tumor suppressor gene therapy induces apotosis and suppreses growth of human pancreatic cancer [ J ] .Ann Surg Oncol,1998,5(8) :681 -688.

共引文献1

同被引文献96

  • 1兰斌,刘炳亚,朱正纲.PLK1在细胞周期生物学的研究进展[J].医学分子生物学杂志,2005,2(1):65-67. 被引量:15
  • 2周琼,白明,苏远.Polo-like激酶1反义RNA对肺癌细胞A549细胞周期的影响[J].癌症,2005,24(2):149-154. 被引量:2
  • 3Mulero-Navarro S, Esteller M. Epigenetic biomarkers for human cancer: the time is now [ J ]. Crit Rev Oncol Hematol, 2008,68(1) :1 -11.
  • 4Abreu PA, Dellamora-Ortiz G, Leao-Ferreira LR, et al. DNA methylation : a promising target for the twenty-first century[ J]. Expert Opin Ther Targets,2008,12(8) :1035 - 1047.
  • 5Szyf M, Pakneshan P, Rabbani SA. DNA methylation and breast cancer [ J ] . Biochem Pharmacol, 2004, 68 ( 6 ) : 1187 -1197.
  • 6Metge BJ, Frost AR, King JA, et al. Epigenetic silencing contributes to the loss of BRMS 1 expression in breast cancer [J]. Clin Exp Metastasis,2008,25(7) :753 -763.
  • 7Bogani C, Ponziani V, Guglielmelli P, et al. Hypermethylation of CXCR4 promoter in CD34 + cells from patients with primary myelofibrosis [ J ]. Stem Cells, 2008, 26 ( 8 ) : 1920- 1930.
  • 8Samant RS, Clark DW, Fillmore RA, et al. Breast cancer metastasis suppressor 1 ( BRMS 1 ) inhibits osteopontin transcription by abrogating NF-kappaB activation [ J ]. Mol Cancer,2007,6:6.
  • 9Phadke PA, Vaidya KS, Nash KT, et al. BRMS1 suppresses breast cancer experimental metastasis to multiple organs by inhibiting several steps of the metastatic process [ J ] . Am J Pathol,2008,172(3) :809-817.
  • 10Muller A, Homey B, Soto H, et al. Involvement of chemokine receptors in breast cancer metastasis [ J ]. Nature, 2001,410(6824) :50 -56.

引证文献6

二级引证文献16

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部