• 西安交通大學醫(yī)學院第一附屬醫(yī)院普通外科(陜西西安 710061);

目的  探討抑癌基因Ras相關區(qū)域家族1A (RASSF1A)基因在結腸癌組織以及相應正常結腸組織中的表達并分析其表達與結腸癌臨床病理因素之間的關系。
方法  采用免疫組織化學SP法和Western blot法檢測34例結腸癌手術標本和相應的正常結腸組織中RASSF1A蛋白的表達水平,應用RT-PCR法檢測RASSF1AmRNA在結腸癌和正常結腸組織中的表達情況。
結果 ?、倜庖呓M織化學法結果:結腸癌組織中RASSF1A蛋白表達陽性率明顯低于其在正常結腸組織中的表達陽性率 〔35.3% (12/34)比97.1% (33/34),P<0.05〕。結腸癌組織中
RASSF1A蛋白的表達與腫瘤分化程度和TNM分期均有關(P<0.05),即高、中分化及TNM分期較低(Ⅰ+Ⅱ期)者的RASSF1A蛋白表達陽性率較高(P<0.05)。②Western blot法結果:在34例結腸癌患者中RASSF1A蛋白表達水平明顯低于其在相應的正常結腸組織中的表達水平 〔0.316 8±0.019 6比0.914 4±0.177 6,P<0.05〕;該結果與RT-PCR法檢測到的RASSF1A mRNA表達情況基本一致 〔0.158 9±0.223 7和0.572 3±0.193 9,P<0.05〕。
結論  RASSF1A基因的失表達可能在原發(fā)性結腸癌的發(fā)生、發(fā)展中起重要作用,檢測RASSF1A的表達情況可為結腸癌的早期診斷提供幫助。

引用本文: 賀賽,孫學軍,鄭見寶,王煒,周培華,魏光兵,王暉,姚建峰,張立,祿韶英,杜俊凱. 抑癌基因RASSF1A在結腸癌中的表達研究△. 中國普外基礎與臨床雜志, 2013, 20(11): 1240-1244. doi: 復制

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19. Lin HH, Ke HL, Huang SP, et al. Increase sensitivity in detectingsuperficial, low grade bladder cancer by combination analysis of hypermethylation of E-cadherin, p16, p14, RASSF1A genes in urine[J]. Urol Oncol, 2010, 28(6):597-602.
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25. Gordon M, Baksh S. RASSF1A:Not a prototypical Ras effector[J]. Small GTPases, 2011, 2(3):148-157.
26. , 15(2):117-127.
  1. 1. László L. Predictive and prognostic factors in the complex treatment of patients with colorectal cancer[J]. Magy Onkol, 2010, 54(4):383-394.
  2. 2. -9.
  3. 3. Xiang TX, Yuan Y, Li LL, et al. Aberrant promoter CpG methyl-ation and its translational applications in breast cancer[J]. Chin J Cancer, 2013, 32(1):12-20.
  4. 4. Van der Weyden L, Papaspyropoulos A, Poulogiannis G, et al. Loss of RASSF1A synergizes with deregulated RUNX2 signaling in tumorigenesis[J]. Cancer Res, 2012, 72(15):3817-3827.
  5. 5. Sherwood V, Recino A, Jeffries A, et al. The N-terminal RASSF family:a new group of Ras-association-domain-containing proteins,with emerging links to cancer formation[J]. Biochem J, 2010, 425(2):303-311.
  6. 6. Guo C, Zhang X, Pfeifer GP. The tumor suppressor RASSF1A prevents dephosphorylation of the mammalian STE20-like kinases MST1 and MST2[J]. J Biol Chem, 2011, 286(8):6253-6261.
  7. 7. Malpeli G, Amato E, Dandrea M, et al. Methylation-associated down-regulation of RASSF1A and up-regulation of RASSF1C in pancreatic endocrine tumors[J]. BMC Cancer, 2011, 11:351. doi:10. 1186/1471-2407-11-351.
  8. 8. Tian Y, Hou Y, Zhou X, et al. Tumor suppressor RASSF1A promoter:p53 binding and methylation[J]. PLoS One, 2011, 6(2):e17017. doi:10.1371/journal.pone.0017017.
  9. 9. Jiang Y, Cui L, Chen WD, et al. The prognostic role of RASSF1Apromoter methylation in breast cancer:a meta-analysis of publisheddata[J]. PLoS One, 2012, 7(5):e36780. doi:10. 1371/journal. pone. 0036780.
  10. 10. 楊雷, 孫學軍, 王煒, 等. MCP-1、VEGF在胃癌中的表達與幽門螺旋桿菌感染的關系[J]. 中國普外基礎與臨床雜志, 2009,.
  11. 11. 鄭見寶, 孫學軍, 王煒, 等. HIF-1α與CDX2在結直腸腺癌組織中的表達及意義[J]. 中國普外基礎與臨床雜志, 2012, 17(12):1265-1269.
  12. 12. Zheng J, Sun X, Wang W, et al. Hypoxia-inducible factor-1alphamodulates the down-regulation of the homeodomain protein CDX2in colorectal cancer[J]. Oncol Rep, 2010, 24(1):97-104.
  13. 13. Wang W, Sun X, Lu L, et al. Cytotoxicity of lymphocytes activ-ated by superantigen toxic-shock-syndrome toxin-1 against colorectal cancer LoVo cells[J]. Mol Cell Biochem, 2013, 376(1-2):.
  14. 14. Saelee P, Wongkham S, Chariyalertsak S, et al. RASSF1A promoter hypermethylation as a prognostic marker for hepatocellular carcinoma[J]. Asian Pac J Cancer Prev, 2010, 11(6):1677-1681.
  15. 15. Dammann R, Li C, Yoon JH, et al. Epigenetic inactivation of a RAS association domain family protein from the lung tumour supp-ressor locus 3p21.3[J]. Nat Genet, 2000, 25(3):315-319.
  16. 16. Montenegro MF, Sáez-Ayala M, Piñero-Madrona A, et al. Reac-tivation of the tumour suppressor RASSF1A in breast cancer by simultaneous targeting of DNA and E2F1 methylation[J]. PLoS One, 2012, 7(12):e52231. doi:10.1371/journal.pone.0052231.
  17. 17. (5):375-378.
  18. 18. Park Y, Kim DS, Park KH, et al. RASSF1A and ERCC1 expre-ssion levels might be predictive of prognosis in advanced, recurrent, and metastatic squamous cell carcinoma of the head and neck treated with docetaxel and cisplatin[J]. Onkologie, 2012, 35(11):673-682.
  19. 19. Lin HH, Ke HL, Huang SP, et al. Increase sensitivity in detectingsuperficial, low grade bladder cancer by combination analysis of hypermethylation of E-cadherin, p16, p14, RASSF1A genes in urine[J]. Urol Oncol, 2010, 28(6):597-602.
  20. 20. Martins AT, Monteiro P, Ramalho-Carvalho J, et al. High RASSF1A promoter methylation levels are predictive of poor prog-nosis in fine-needle aspirate washings of breast cancer lesions[J]. Breast Cancer Res Treat, 2011, 129(1):1-9.
  21. 21. Ghazaleh HA, Chow RS, Choo SL, et al. 14-3-3 mediated regulation of the tumor suppressor protein, RASSF1A[J]. Apoptosis,.
  22. 22. Richter AM, Pfeifer GP, Dammann RH. The RASSF proteins in cancer;from epigenetic silencing to functional characterization[J]. Biochim Biophys Acta, 2009, 1796(2):114-128.
  23. 23. 顧全凱, 閆慶輝, 王鳳安, 等. TIMP-3和RASSF1A在大腸癌中的表達及臨床意義[J]. 世界華人消化雜志, 2012, 20(27):2642-2647.
  24. 24. Thaler S, Hähnel PS, Schad A, et al. RASSF1A mediates p21Cip1/Waf1-dependent cell cycle arrest and senescence through modulation of the Raf-MEK-ERK pathway and inhibition of Akt[J]. Cancer Res, 2009, 69(5):1748-1757.
  25. 25. Gordon M, Baksh S. RASSF1A:Not a prototypical Ras effector[J]. Small GTPases, 2011, 2(3):148-157.
  26. 26. , 15(2):117-127.