期刊文献+

Wnt/β-catenin信号通路在实验性大鼠肝癌形成过程中的作用 被引量:11

Role of Wnt/β-catenin signaling transduction pathway in rat hepatocarcinogenesis
下载PDF
导出
摘要 目的:探讨Wnt/β-catenin信号转导通路与肿瘤发生的关系,为肝癌的防治提供新的思路。方法:选取Wnt/β-catenin信号转导通路中上下游关键因子wnt1、β-catenin、APC、cyclinD1以及c-myc等,应用RT-PCR法观察它们在正常肝脏,不典型增生肝脏和肝癌组织中的转录水平。用免疫组化染色法研究β-catenin、APC和cyclinD1等3个因子有无表达。结果:在正常肝脏中,用RT-PCR未检测到wnt1、cyc-linD1以及c-myc的mRNA转录,免疫组化染色也只观察到β-catenin在细胞膜处有比较弱的表达。诱癌14周后,在发生不典型增生的肝组织中,检测到β-catenin、APC和cyclinD13个基因的转录。通过免疫组化染色也观察到β-catenin蛋白在胞质中的积累,APC和cyclinD1在部分细胞中出现表达。诱癌16周后,在肝癌组织中,除wnt1mRNA外,其他几个因子的mRNA都有转录,免疫组化也印证了上述各个发生转录的因子在蛋白水平都有不同程度的表达。结论:Wnt/β-catenin信号转导通路在大鼠的肝癌形成过程中被激活,其可能是实验性肝癌发生的原因之一。 AIM: To investigate the role of Wnt/β-catenin signaling transduction pathway in rat hepatocarcinogenesis. METHODS: The mRNAs of Wnt1, β-catenin, APC, cyclin D1 and c-myc genes were amplified by using of semiquantitative reverse transcription polymerase chain reaction (RT-PCR) from normal rat livers, atypical hyperplasia livers and hepatoma tissues, respectively. Then the proteins expression of β-catenin, APC and cyclin D1 was examined by immunohistochemical staining. RESULTS: In normal rat livers, the mRNAs of Wnt1, cyclin D1 and c-myc genes were not detected and only β-catenin protein was observed to have low expression at cellular membrane. However, 14 weeks after cancer induction in atypical hyperplasia livers, β-catenin protein and APC protein were accumulated in cytoplasm. Meanwhile, cyclin D1 protein was detected in cytoplasm and/or nucleus in some cells. 16 weeks after cancer induction in hepatoma tissues, the mRNAs and protein expression of β-catenin, APC, cyclin D1 and c-myc genes were detected except Wnt1. CONCLUSION: The activation of Wnt/β-catenin signaling transduction pathway might be one of the reasons for rat hepatocarcinogenesis.
出处 《细胞与分子免疫学杂志》 CAS CSCD 北大核心 2006年第4期454-457,共4页 Chinese Journal of Cellular and Molecular Immunology
基金 纽约中华医学基金会(CMB 82-412)
关键词 WNT/Β-CATENIN 信号转导通路 肝癌发生 大鼠 Wnt/β-catenin signaling transduction pathway hepatocarcinogenesis rat
  • 相关文献

参考文献10

  • 1Moon RT,Bowerman B,Boutros M,et al.The promise and perils of Wnt signaling through beta-catenin[J].Science,2002,296(5573):1644-1646.
  • 2Kobayashi M,Honma T,Matsuda Y,et al.Nuclear translocation of beta-catenin in colorectal cancer[J].Br J Cancer,2000,82(10):1689-1693.
  • 3郑杰,武忠弼,阮幼冰,刘冰.二乙基亚硝胺诱发大鼠肝癌前病变中c-myc、N-ras和γ-GT酶表达的相关性研究[J].肿瘤,1995,15(6):462-465. 被引量:3
  • 4Maruyama K,Ochiai A,Akimato S.Cytoplasmic β-catenin accumulation as a spredictor of hematogenous metastasis in human colorectal cancer[J].Oncology,2000,59(4):302-309.
  • 5Pennisi E.How a growth control path takes a wrong turn to cancer[J].Seience,1998,281(5382):1438-1441.
  • 6范恺谊,尹淼,朱晓群,徐莺莺,申宗侯.肝癌SMMC-7721细胞中PKB对β-连环蛋白的调控[J].复旦学报(医学版),2004,31(5):445-448. 被引量:1
  • 7Polakis P.Wnt signaling and cancer[J].Genes Dev,2000,14(15):1837-1851.
  • 8van de W etering M,Barker N,Harkes IC,et al.Mutant E-cadherin breast cancer cells do not display constitutivewnt signaling[J].Cancer Res,2001,61(1):278-284.
  • 9刘丽萍,于卉影,马东初.eIF4E的研究进展[J].细胞与分子免疫学杂志,2005,21(B03):118-121. 被引量:6
  • 10Chesire DR,Ewing CM,Sauvageot J,et al.Detection and analysis of β-catenin mutations in prostate cancer[J].Prostate,2000,45(4):323-334.

二级参考文献39

  • 1Strudwick S, Borden KL. The emerging roles of translation factor eIF4E in the nucleus[J]. Differentiation, 2002, 70(1): 10-22.
  • 2Iborra FJ, Jackson DA, Cook PR. Coupled transcription and translation within nuclei of mammalian cells[J]. Science, 2001, 293(5532): 1139-1142.
  • 3Nathanson L, Xia T, Deutscher MP. Nuclear protein synthesis: A re-evaluation[J]. RNA, 2003, 9(1): 9-13.
  • 4Dahlberg JE, Lund E, Goodwin EB. Nuclear translation: what is the evidence?[J]. RNA, 2003, 9(1): 1-8.
  • 5Rosenwald IB. The role of translation in neoplastic transformation from a pathologist's point of view[J]. Oncogene, 2004, 23(18): 3230-3247.
  • 6De Benedetti A, Graff JR. eIF-4E expression and its role in malignancies and metastases[J]. Oncogene, 2004, 23(18): 3189-3199.
  • 7Schmidt EV. The role of c-myc in regulation of translation initiation[J]. Oncogene, 2004, 23(18): 3217-3221.
  • 8Ivan Topisirovic ML, Guzman MJ, McConnell JD, et al. Aberrant eukaryotic translation initiation factor 4E-dependent mRNA transport impedes hematopoietic differentiation and contributes to leukemogenesis[J]. Mol Cell Biol, 2003, 23(24): 8992-9002.
  • 9Wang X, Flynn A, Waskiewicz AJ, et al. The phosphorylation of eukaryotic initiation factor eIF4E in response to phorbol esters, cell stresses, and cytokines is mediated by distinct MAP kinase pathways[J]. J Biol Chem, 1998, 273(16): 9373-9377.
  • 10Scheper GC, Morrice NA, Kleijn M, et al. The mitogen-activated protein kinase signal-integrating kinase Mnk2 is a eukaryotic initiation factor 4E kinase with high levels of basal activity in mammalian cells[J]. Mol Cell Biol, 2001, 21(3): 743-754.

共引文献7

同被引文献58

引证文献11

二级引证文献65

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