期刊文献+

磷酸化mTOR在胆囊癌中的表达及其临床意义 被引量:1

Expression of activated mTOR in gallbladder carcinoma tissue and its clinical significance
下载PDF
导出
摘要 目的:探讨磷酸化雷帕霉素哺乳动物靶标(phosphorylate-mammalian target of rapamycin,p-mTOR)在人胆囊癌组织中的表达及其临床意义。方法:应用组织芯片技术和免疫组织化学(EnVision)方法检测来自上海市浦东新区人民医院外科和第二军医大学长征医院肿瘤科2004-2007年间6例慢性胆囊炎、7例癌旁组织和59例胆囊癌组织中p-mTOR的表达,并分析其与胆囊癌浸润深度、分化、Nevin分期等病理特征之间的相关性。结果:p-mTOR在慢性胆囊炎组织、癌旁组织和癌组织中表达的阳性率分别为0、0和47.5%,表达差异有统计学意义(P<0.01)。p-mTOR在分化高、中和低/未分化的胆囊癌组织中阳性表达率分别为21.4%、48.1%和66.7%(P<0.01);在浸润至黏膜层/肌层、浆膜层和周围组织的胆囊癌组织中, p-mTOR的阳性表达率分别为30.0%、35.7%和71.4%(P<0.01);p-mTOR在Ⅰ/Ⅱ期、Ⅲ/Ⅳ期和Ⅴ期胆囊癌组织中的阳性表达率分别为11.1%、46.4%和66.7%,呈明显上升趋势(P<0.01)。结论:p-mTOR的表达与人胆囊癌的浸润深度、组织分化和Nevin分期密切相关,p-mTOR可能参与人胆囊癌的发生发展过程。 Objective:To investigate the expression of phosphorylate-mammalian target of rapamycin, p-mTOR, in human gallbladder carcinoma and its clinical significance. Methods: Six chronic cholecystitis tissues, 7 adjacent gallbladder carcinoma tissues and 59 gallbladder carcinoma tissues, obtained from Department of General Surgery, People's Hospital of Pudong New Area and Department of Oncology of Changzheng Hospital from 2004 to 2007, were evaluated by immunohistochemistry and tissue microarray for p-mTOR expression. The correlations among p-roTOR expression with gallbladder carcinoma invasion, differentiation and Nevin stage were analyzed. Results: The positive rates of p-mTOR in chronic cholevstitis, adjacent-neoplatic gallbladder carcinoma and gallbladder carcinoma tissue were 0, 0 and 47.5% , respectively ( P 〈 0.01 ). The positive rates of p-roTOR in with well-, moderately- and poorly-differentiated gallbladder carcinoma tissues were 21.4%, 48.1% and 66.7%, respectively; there were a significant differences among the three groups(P 〈 0.01 ). The positive rates in gallbladder carcinoma tissue with mucosa and muscle invasion, serous membrane invasion and peripheral tissue invasion were 30% , 35.7 % and 71.40% , respectively ( P 〈 0.01 ). The positive rates in Ⅰ/Ⅱ,Ⅲ/Ⅳ and Ⅴ stage gallbladder carcinoma tissues were 11.1%, 46.4% and 66.7%, respectively, showing a significant increasing trend( P 〈0.01 ). Conclusion: The expression of p-mTOR is closely related with low differentiation, invasion and clinical stage ( Nevin stage) of gallbladder carcinoma and may participate in the development and progression of gallbladder carcinoma.
出处 《中国肿瘤生物治疗杂志》 CAS CSCD 2008年第6期571-574,共4页 Chinese Journal of Cancer Biotherapy
关键词 磷酸化雷帕霉素哺乳动物靶标 胆囊癌 组织芯片 phosphorylate mammalian target of rapamycin (p-roTOR) gallbladder neoplasms tissue microarray
  • 相关文献

参考文献1

二级参考文献136

  • 1Gao X, Zhang Y, Arrazola P, et al. Tsc tumour suppressor proteins antagonize amino-acid-TOR signalling. Nat Cell Biol 2002; 4:699-704.
  • 2Potter C J, Pedraza LG, Xu T. Akt regulates growth by directly phosphorylating Tsc2. Nat Cell Biol 2002; 4:658-665.
  • 3Goncharova EA, Goncharov DA, Eszterhas A, et al. Tuberin regulates p70 S6 kinase activation and ribosomal protein S6 phosphorylation. A role for the TSC2 tumor suppressor gene in pulmonary lymphangioleiomyomatosis (LAM). J Biol Chem 2002; 277:30958-30967.
  • 4Inoki K, Li Y, Zhu T, Wu J, Guan KL. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol 2002; 4:648-657.
  • 5Potter C J, Huang H, Xu T. Drosophila Tsc I functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size. Cell 2001; 105:357-368.
  • 6Tapon N, Ito N, Dickson B J, Treisman JE, Hariharan IK. The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation. Cell 2001; 105:345-355.
  • 7Gao X, Pan D. TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth. Genes Dev 2001; 15:1383-1392.
  • 8Radimerski T, Montagne J, Hemmings-Mieszczak M, Thomas G. Lethality of Drosophila lacking TSC tumor suppressor function rescued by reducing dS6K signaling. Genes Dev 2002; 16:2627-2632.
  • 9Tee AR, Fingar DC, Manning BD, Kwiatkowski DJ, Cantley LC, Blenis J. Tuberous sclerosis complex- 1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling. Proc Natl Acad Sci USA 2002; 99:13571-13576.
  • 10Sabatini DM, Erdjument-Bromage H, Lui M, Tempst P, Snyder SH. RAFT 1: a mammalian protein that binds to FKBP 12 in a rapamycin-dependent fashion and is homologous to yeast TORs. Cell 1994; 78:35-43.

共引文献50

同被引文献15

  • 1Lang SA, Gaumann A, Koehl GE, et al. Mammalian target of rapamycin is activated in human gastric cancer and serves as a targel for therapy in an experimental model [J]. lnt J Cancer, 2007, 120(8) : 1803-1810.
  • 2Elit L. Drug evaluation: AP-23573--an roTOR inhibitor for the treatment of cancer [ J ]. Drugs, 2006, 9 (9) : 636-644.
  • 3Kim SH, Zukowski K, Novak RF. Rapamyein effects on roTOR signaling in benign, premalignant and malignant human breast epithelial cells [ J ]. Anticancer Res, 2009, 29 (4) : 1143-1150.
  • 4Alley MC, Scudiero DA, Monks A, et al. Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay [J].Cancer Res. 1988,48 (3) : 589-601.
  • 5Lu KP, Means AR. Regulation of the cell cycle and calmodulin [J]. EndocrRev, 1993, 14(1): 40-48.
  • 6Michallet MC, Sahel F, Flacher M, et al. Cathepsin-dsependent apoptosis triggered hy supraoptimal activation of T lymphocytes: a possible mechanism of high dose tolerance [J]. J Immunology, 2004, 172 (9) : 5405-5414.
  • 7Peng TL, Chert J, Mao W, et al. Aryl hydrocarbon receptor pathway activation enhances gastric cancer cell invasiveness likely through a c-Jun-dependent induction of matrix metalloproteinase-9 [J]. BMC Cell Biol, 2009, 10(1): 27.
  • 8Kidd M, Eiek GN, Modlin IM, et al. Further delineation of the continuous Imman neoplastic enteroehromaffin cell line, KRJ-1, and the inhibitory effects of lanreotide and rapamycin [J].J Mol Endo, 2007, 38(1-2) : 181-192.
  • 9Hassid VJ, Orlando FA, Awad ZT, et al. Genetic and molecular abnormalities in cholangiocarcinogenesis [J]. Anlicancer Res, 2009, 29(4) : 1151-1156.
  • 10Lang SA, Gaumann A, Koehl GE, et al. Mammalian target of rapamycin is activated in human gastric cancer and serves as a target for therapy in an experimental model[J].Int J Cancer, 2007, 120(8) : 1803-1810.

引证文献1

二级引证文献2

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