• 上海交通大學(xué)附屬第一人民醫(yī)院普外科（上海 200080）;

目的  探討胃癌組織中Runt相關(guān)轉(zhuǎn)錄因子3（Runx3）基因的表達(dá)情況及其與胃癌臨床病理學(xué)因素的關(guān)系。方法  采用逆轉(zhuǎn)錄-聚合酶鏈反應(yīng)（RT-PCR）和蛋白印跡（Western blot）法分別檢測(cè)52例胃癌組織和配對(duì)的正常胃黏膜組織中Runx3 mRNA以及蛋白的表達(dá)水平，并分析Runx3表達(dá)與胃癌臨床病理學(xué)因素的關(guān)系。結(jié)果  59.6%(31/52)的胃癌組織出現(xiàn)Runx3 mRNA表達(dá)缺失，48.1%（25/52）出現(xiàn)Runx3蛋白表達(dá)缺失，其缺失率均明顯高于對(duì)應(yīng)的正常胃黏膜組織（P＜0.05）。Runx3的表達(dá)缺失與腫瘤大小、組織分化程度、浸潤(rùn)深度、淋巴結(jié)轉(zhuǎn)移及TNM分期有關(guān)（P＜0.05，P＜0.01）。Runx3 mRNA表達(dá)與蛋白表達(dá)呈正相關(guān)（r=0.840，P＜0.01）。結(jié)論  Runx3基因與胃癌的發(fā)生、發(fā)展密切相關(guān)，有望成為胃癌診斷和治療的新靶點(diǎn)。

引用本文： 張建海,李利義,李繼坤. 抑癌基因Runt相關(guān)轉(zhuǎn)錄因子3在胃癌中的表達(dá)及其與臨床病理學(xué)因素的關(guān)系. 中國(guó)普外基礎(chǔ)與臨床雜志, 2008, 15(11): 840-843. doi: 復(fù)制

1. Bangsow C, Rubins N, Glusman G, et al. The RUNX3 gene-sequence, structure and regulated expression [Ｊ]. Gene, 2001; 279(2)∶221.
2. Waki T, Tamura G, Sato M, et al. Promoter methylation status of DAP-kinase and RUNX3 genes in neoplastic and non-neoplastic gastric epithelia [Ｊ]. Cancer Sci, 2003; 94(4)∶360.
3. Kim TY, Lee HJ, Hwang KS, et al. Methylation of RUNX3 in various types of human cancers and premalignant stages of gastric carcinoma [Ｊ]. Lab Invest, 2004; 84(4)∶479.
4. Miyazono K, Maeda S, Imamura T. Coordinate regulation of cell growth and differentiation by TGF-beta superfamily and Runx proteins [Ｊ]. Oncogene, 2004; 23(24)∶4232.
5. Kim WJ, Kim EJ, Jeong P, et al. RUNX3 inactivation by point mutations and aberrant DNA methylation in bladder tumors [Ｊ]. Cancer Res, 2005; 65(20)∶9347.
6. Park WS, Cho YG, Kim CJ, et al. Hypermethylation of the RUNX3 gene in hepatocellular carcinoma [Ｊ]. Exp Mol Med, 2005; 37(4)∶276.
7. Goel A, Arnold CN, Tassone P, et al. Epigenetic inactivation of RUNX3 in microsatellite unstable sporadic colon cancers [Ｊ]. Int J Cancer, 2004; 112(5)∶754.
8. Wada M, Yazumi S, Takaishi S, et al. Frequent loss of RUNX3 gene expression in human bile duct and pancreatic cancer cell lines [Ｊ]. Oncogene, 2004; 23(13)∶2401.
9. Xiao WH, Liu WW. Hemizygous deletion and hypermethylation of RUNX3 gene in hepatocellular carcinoma [Ｊ]. World J Gastroenterol, 2004; 10(3)∶376.
10. Ku JL, Kang SB, Shin YK, et al. Promoter hypermethylation downregulates RUNX3 gene expression in colorectal cancer cell lines [Ｊ]. Oncogene, 2004; 23(40)∶6736.
11. Yanada M, Yaoi T, Shimada J, et al. Frequent hemizygous deletion at 1p36 and hypermethylation downregulate RUNX3 expression in human lung cancer cell lines [Ｊ]. Oncol Rep, 2005; 14(4)∶817.
12. Sato K, Tomizawa Y, Iijima H, et al. Epigenetic inactivation of the RUNX3 gene in lung cancer [Ｊ]. Oncol Rep, 2006; 15(1)∶129.
13. Lund AH, van Lohuizen M. RUNX: a trilogy of cancer genes [Ｊ]. Cancer Cell, 2002; 1(3)∶213.
14. Li QL, Ito K, Sakakura C, et al. Causal relationship between the loss of RUNX3 expression and gastric cancer [Ｊ]. Cell, 2002; 109(1)∶113.
15. Fukamachi H, Ito K. Growth regulation of gastric epithelial cells by Runx3 [Ｊ]. Oncogene, 2004; 23(24)∶4330.
16. Otto F, Lübbert M, Stock M. Upstream and downstream targets of RUNX proteins [Ｊ]. J Cell Biochem, 2003; 89(1)∶9.
17. Heldin CH, Miyazono K, ten Dijke P. TGF-beta signalling from cell membrane to nucleus through SMAD proteins [Ｊ]. Nature, 1997; 390(6659)∶465.
18. Osaki M, Moriyama M, Adachi K, et al. Expression of RUNX3 protein in human gastric mucosa, intestinal metaplasia and carcinoma [Ｊ]. Eur J Clin Invest, 2004; 34(9)∶605.
19. Guo WH, Weng LQ, Ito K, et al. Inhibition of growth of mouse gastric cancer cells by Runx3, a novel tumor suppressor [Ｊ]. Oncogene, 2002; 21(54)∶8351.
20. Wei D, Gong W, Oh SC, et al. Loss of RUNX3 expression significantly affects the clinical outcome of gastric cancer patients and its restoration causes drastic suppression of tumor growth and metastasis [Ｊ]. Cancer Res, 2005; 65(11)∶4809.
  1. 1. Bangsow C, Rubins N, Glusman G, et al. The RUNX3 gene-sequence, structure and regulated expression [Ｊ]. Gene, 2001; 279(2)∶221.
  2. 2. Waki T, Tamura G, Sato M, et al. Promoter methylation status of DAP-kinase and RUNX3 genes in neoplastic and non-neoplastic gastric epithelia [Ｊ]. Cancer Sci, 2003; 94(4)∶360.
  3. 3. Kim TY, Lee HJ, Hwang KS, et al. Methylation of RUNX3 in various types of human cancers and premalignant stages of gastric carcinoma [Ｊ]. Lab Invest, 2004; 84(4)∶479.
  4. 4. Miyazono K, Maeda S, Imamura T. Coordinate regulation of cell growth and differentiation by TGF-beta superfamily and Runx proteins [Ｊ]. Oncogene, 2004; 23(24)∶4232.
  5. 5. Kim WJ, Kim EJ, Jeong P, et al. RUNX3 inactivation by point mutations and aberrant DNA methylation in bladder tumors [Ｊ]. Cancer Res, 2005; 65(20)∶9347.
  6. 6. Park WS, Cho YG, Kim CJ, et al. Hypermethylation of the RUNX3 gene in hepatocellular carcinoma [Ｊ]. Exp Mol Med, 2005; 37(4)∶276.
  7. 7. Goel A, Arnold CN, Tassone P, et al. Epigenetic inactivation of RUNX3 in microsatellite unstable sporadic colon cancers [Ｊ]. Int J Cancer, 2004; 112(5)∶754.
  8. 8. Wada M, Yazumi S, Takaishi S, et al. Frequent loss of RUNX3 gene expression in human bile duct and pancreatic cancer cell lines [Ｊ]. Oncogene, 2004; 23(13)∶2401.
  9. 9. Xiao WH, Liu WW. Hemizygous deletion and hypermethylation of RUNX3 gene in hepatocellular carcinoma [Ｊ]. World J Gastroenterol, 2004; 10(3)∶376.
  10. 10. Ku JL, Kang SB, Shin YK, et al. Promoter hypermethylation downregulates RUNX3 gene expression in colorectal cancer cell lines [Ｊ]. Oncogene, 2004; 23(40)∶6736.
  11. 11. Yanada M, Yaoi T, Shimada J, et al. Frequent hemizygous deletion at 1p36 and hypermethylation downregulate RUNX3 expression in human lung cancer cell lines [Ｊ]. Oncol Rep, 2005; 14(4)∶817.
  12. 12. Sato K, Tomizawa Y, Iijima H, et al. Epigenetic inactivation of the RUNX3 gene in lung cancer [Ｊ]. Oncol Rep, 2006; 15(1)∶129.
  13. 13. Lund AH, van Lohuizen M. RUNX: a trilogy of cancer genes [Ｊ]. Cancer Cell, 2002; 1(3)∶213.
  14. 14. Li QL, Ito K, Sakakura C, et al. Causal relationship between the loss of RUNX3 expression and gastric cancer [Ｊ]. Cell, 2002; 109(1)∶113.
  15. 15. Fukamachi H, Ito K. Growth regulation of gastric epithelial cells by Runx3 [Ｊ]. Oncogene, 2004; 23(24)∶4330.
  16. 16. Otto F, Lübbert M, Stock M. Upstream and downstream targets of RUNX proteins [Ｊ]. J Cell Biochem, 2003; 89(1)∶9.
  17. 17. Heldin CH, Miyazono K, ten Dijke P. TGF-beta signalling from cell membrane to nucleus through SMAD proteins [Ｊ]. Nature, 1997; 390(6659)∶465.
  18. 18. Osaki M, Moriyama M, Adachi K, et al. Expression of RUNX3 protein in human gastric mucosa, intestinal metaplasia and carcinoma [Ｊ]. Eur J Clin Invest, 2004; 34(9)∶605.
  19. 19. Guo WH, Weng LQ, Ito K, et al. Inhibition of growth of mouse gastric cancer cells by Runx3, a novel tumor suppressor [Ｊ]. Oncogene, 2002; 21(54)∶8351.
  20. 20. Wei D, Gong W, Oh SC, et al. Loss of RUNX3 expression significantly affects the clinical outcome of gastric cancer patients and its restoration causes drastic suppression of tumor growth and metastasis [Ｊ]. Cancer Res, 2005; 65(11)∶4809.