期刊文献+

哺乳动物雷帕霉素靶蛋白信号通路及其下游蛋白在胃癌组织中的活化及临床意义 被引量:6

Activation and its clinical significance of the mammalian target of rapamycin pathway and its downstream proteins in gastric cancer
原文传递
导出
摘要 目的研究哺乳动物雷帕霉素靶蛋白(mTOR)信号通路相关蛋白mTOR和真核起始因子4E结合蛋白1(4E-BP1)在胃癌组织中的活化情况及其临床意义。方法利用免疫组织化学技术观察38例手术患者胃癌组织中mTOR和4E-BP1的活化情况,采用卡方检验及Kruskal-Wallis检验分析磷酸化mTOR及4E-BP1在癌区、癌旁和正常胃黏膜组织中表达的差异,以及各种临床病理参数间的表达差异。结果磷酸化mTOR在胃癌组织中的阳性表达率高于匹配的癌旁及正常组织[71.1%(27/38)比50.0%(19/38)比44.7%(17/38);X^2=11.031,P=0.026],其下游的4E-BP1在胃癌组织中的阳性表达率也高于匹配的癌旁及正常组织[68.4%(26/38)比57.9%(22/38)比28.9%(11/38);X^2=13.943,P=0.007]。磷酸化mTOR和4E-BP1与肿瘤Lauren's分型、浸润分期、分化程度、淋巴结转移及患者年龄等无关,但胃癌组织中活化的4E-BP1在不同大小肿瘤间表达差异有统计学意义(H=3.86,P〈0.05)。结论mTOR信号通路在胃癌发生中存在过度激活,其下游蛋白4e-BP1磷酸化程度在不同大小肿瘤中存在差异。 Objective To investigate the activation and clinical significance of the mammalian target of rapamycin (mTOR) pathway related protein and eukaryotic translation factor 4E-binding protein 1 (4E-BP1) in gastric cancer. Methods The activation of roTOR and 4E-BP1 in gastric cancer tissues of 38 surgical patients were detected by immunohistochemical method. The differences of phosphorylated mTOR and 4E-BP1 expression among cancerous tissues, para-cancerous tissues and normal gastric mucosa tissues and dinicopathological variables were analyzed by Chi square test and Kruskal-Wallis test. Results The positive expression rate of phosphorylated mTOR in the gastric cancerous tissues was significantly higher than that of para-cancerous tissues and normal tissues [71.1% (27/ 38), 50.0%(19/38) and 44.7% (17/38), X^2 = 11.031, P= 0.026]. The positive expression rate of downstream protein 4E-BP1 in the gastric cancer tissues was also significantly higher than that of para- cancerous tissues and normal tissues [68.40%(26/38), 57.9%(22/38) and 28.9%(11/38),X^2=13.943, P=0.007]. There was no correlation between phosphorylated roTOR and 4E-BP1 expression and tumor Lauren's sub-type, infiltration, differentiation degree, lymph node metastasis and patient's age. There was statistical significant difference between activated 4E-BP1 expression and tumor size in gastric cancer (H=3.86, P〈0.05). Conclusions mTOR pathway was over activated in gastric cancer. There was difference between phosphorylation degree of its downstream protein 4E-BP1 and the tumor size.
出处 《中华消化杂志》 CAS CSCD 北大核心 2013年第3期166-170,共5页 Chinese Journal of Digestion
基金 国家自然科学基金青年科学基金(81001070)
关键词 西罗莫司 蛋白质丝氨酸苏氨酸激酶 信号转导 真核细胞起始因子4E 胃肿瘤 Sirolimus Protein-serine-threonine kinases Signal transduction Eukaryotic initiation factor 4E Stomach neoplasms
  • 相关文献

参考文献10

  • 1Lang 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. Int J Cancer, 2007,120:1803-1810. 被引量:1
  • 2Al-Batran SE, Ducreux M, Ohtsu A. mTOR as a therapeutic target in patients with gastric cancer. Int J Cancer, 2012,130:491-496. 被引量:1
  • 3Hudes G, Cardueci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med, 2007, 356: 2271-2281. 被引量:1
  • 4Phung TL, Ziv K, Dabydeen D, et al. Pathological angiogenesis is induced by sustained Akt signaling and inhibited by raparaycin. Cancer Cell, 2006,10 : 159-170. 被引量:1
  • 5Atkins MB, Hidalgo M, Stadler WM, et al. Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advaneed refractory renal cell carcinoma. J Clin Oneol, 2004,22,909-918. 被引量:1
  • 6Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell, 2012,149: 274-293. 被引量:1
  • 7Armengol G, Rojo F, Castellvl J, et al. 4E-binding protein 1: a key molecular " funnel factor" in human cancer with clinical implications. Cancer Res, 2007,67 : 7551-7555. 被引量:1
  • 8Fuereder T, Jaeger-Lansky A, Hoeflmayer D,et al. mTOR inhibition by everolimus counteracts VEGF induction by sunitinib and improves anti-tumor activity against gastric cancer in vivo. Cancer Lett, 2010,296:249-256. 被引量:1
  • 9Sahin F, Kannangai R, Adegbola O, et al. mTOR and P70S6 kinase expression in primary liver neoplasms. Clin Cancer Res, 2004,10:8421-8425. 被引量:1
  • 10Zhou X, Tan M, Stone Hawthorne V, et al. Activation of the Akt/mammalian target of rapamyein/4E-BP1 pathway by ErbB2 overexpression predicts tumor progression in breast cancers. Clin Cancer Res, 2004,10:6779-6788. 被引量:1

同被引文献50

  • 1罗治文,谢笑娟,马桂兰,呼建文,刘丽杰,葛文松,朱樑.胃癌及癌旁组织定量比较蛋白质组学研究[J].中国生物工程杂志,2007,27(7):55-60. 被引量:7
  • 2黄文斌,张丽华,陈洁宇,周晓军.胃癌组织差异蛋白表达谱的初步研究[J].医学研究生学报,2007,20(9):940-943. 被引量:9
  • 3Brenner B,Hoshen MB,Purim O,David MB,Ashkenazi K,Marshak G,Kundel Y,Brenner R,Morgenstern S,Halpern M,Rosenfeld N,Chajut A,Niv Y,Kushnir M.MicroRNAs as a potential prognostic factor in gastric cancer.World J Gastroenterol 2011;17:3976-3985. 被引量:1
  • 4Jemal A,Bray F,Center MM,Ferlay J,Ward E,Forman D.Global cancer statistics.CA Cancer J Clin 2011;61:69-90. 被引量:1
  • 5Lee KW,Park SR,Oh DY,Park YI,Khosravan R,Lin X,Lee SY,Roh EJ,Valota O,Lechuga MJ,Bang YJ.Phase I study of sunitinib plus capecitabine/cisplatin or capecitabine/oxaliplatin in advanced gastric cancer.Invest New Drugs 2013;31:1547-1558. 被引量:1
  • 6Scott KL,Kabbarah O,Liang MC,Ivanova E,Anagnostou V,Wu J,Dhakal S,Wu M,Chen S,Feinberg T,Huang J,Saci A,Widlund HR,Fisher DE,Xiao Y,Rimm DL,Protopopov A,Wong KK,Chin L.GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer.Nature 2009;459:1085-1090. 被引量:1
  • 7Hu BS,Hu H,Zhu CY,Gu YL,Li JP.Overexpression of GOLPH3 is associated with poor clinical outcome in gastric cancer.Tumour Biol 2013;34:515-520. 被引量:1
  • 8Bell AW,Ward MA,Blackstock WP,Freeman HN,Choudhary JS,Lewis AP,Chotai D,Fazel A,Gushue JN,Paiement J,Palcy S,Chevet E,Lafrenière-Roula M,Solari R,Thomas DY,Rowley A,Bergeron JJ.Proteomics characterization of abundant Golgi membrane proteins.J Biol Chem 2001;276:5152-5165. 被引量:1
  • 9Dippold HC,Ng MM,Farber-Katz SE,Lee SK,Kerr ML,Peterman MC,Sim R,Wiharto PA,Galbraith KA,Madhavarapu S,Fuchs GJ,Meerloo T,Farquhar MG,Zhou H,Field SJ.GOLPH3 bridges phosphatidylinositol-4- phosphate and actomyosin to stretch and shape the Golgi to promote budding.Cell 2009;139:337-351. 被引量:1
  • 10Schmitz KR,Liu J,Li S,Setty TG,Wood CS,Burd CG,Ferguson KM.Golgi localization of glycosyltransferases requires a Vps74p oligomer.Dev Cell 2008;14:523-534. 被引量:1

引证文献6

二级引证文献5

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