期刊文献+

TGFβ1与Smad 4基因在肝细胞癌中的表达及意义 被引量:1

Expression and Significance of TGFβ1 and Smad 4 Gene in Human Hepatocellular Carcinoma Tissues
下载PDF
导出
摘要 目的探讨TGFβ-Smad信号通路中TGFβ1与Co-Smad(Smad 4)与肝细胞癌的发生、发展的关系。方法采用免疫组化ABC法及原位杂交法(ISH),检测41例肝细胞癌组织与癌旁组织中TGFβ1、Smad 4蛋白、Smad 4 mRNA的表达,以5例外伤性肝破裂手术切除标本作为正常对照。比较HCC组与对照组及HCC癌旁中TGFβ1与Smad 4蛋白、Smad 4 mRNA表达的差异,并进行图像分析。结果正常对照组中TGFβ1呈阴性表达,Smad 4蛋白、Smad 4 mRNA均呈阳性表达;HCC组织中TGFβ1阳性表达率为78.0%(32/41),癌旁组织中为95.1%(39/41),两者比较差异显著(P<0.05);Smad 4蛋白在HCC组织中阳性表达率为48.8%(20/41),在癌旁组织中为78.0%(32/41),两者比较有显著性差异(P<0.01);Smad 4 m RNA在HCC组织中阳性表达率为51.2%(21/41),在癌旁组织中为73.1%(30/41),两者比较有显著性差异(P<0.05);与正常肝组织比较,HCC组织中Smad 4蛋白和Smad 4 mRNA阳性表达率均显著降低(P<0.05);Ⅰ、Ⅱ级HCC组织与Ⅲ、Ⅳ级HCC组织Smad 4 m RNA阳性表达存在显著差异(P<0.05),Ⅲ、Ⅳ级阳性表达率较Ⅰ、Ⅱ级降低;Smad 4蛋白的阳性面积百分比、光密度及Smad 4 m RNA的阳性面积百分比癌旁组织均显著高于HCC组织(P均<0.05)。HCC组织中Smad 4蛋白、Smad 4 m RNA表达与TGF-β1表达比较均存在显著差异(P<0.05),但均无显著相关性(P>0.05)。结论TGFβ1过表达、Smad 4表达缺失可能在肝细胞癌的发生、发展中发挥重要作用。 Objective To investigate the correlation between the expression of TGFβ1, Smad 4 genes and the carcinogenesis and tumor progression of human hepatocellular carcinoma (HCC). Methods IHC and ISH method was used to detect the expression of TGFβ1, Smad 4 protein and Smad 4 mRNA in the specimens from 41 HCC and the adjacent liver tissues. Tissues from 5 traumatic livers were used as normal control. Results TGFβ1 expression was negative, but Smad 4 protein and Smad 4 mRNA were positively expressed in normal liver tissues. The positive expression of TGFβ1, Smad 4 and Smad 4 mRNA was detected in the tissues from 32 cases(78.0%),20 cases (48.8%) and 21 cases (51.2%) with HCC,and 39(95. 1%),32 (78.0%) and 30 (73.1% ) adjacent liver tissues. The expression rate of TGFβ1, Smad 4 protein and Smad 4 protein was significantly different between the HCC and adjacent liver tissues (P 〈 0.05 ). The expression of Smad 4 mRNA in HCC tissues was significantly lower in gradeⅢ - Ⅳthan that in grade Ⅰ- Ⅱ( P 〈 0.05 ). Conclusion The over - expression of TGFβ1 and the lower - expression of Smad 4 genes may play an important role in occurrence and progression of HCC.
出处 《实用癌症杂志》 2009年第5期473-476,共4页 The Practical Journal of Cancer
关键词 肝细胞癌 TGFΒ1基因 SMAD 4基因 免疫组织化学 原位杂交 Hepatocellular carcinoma TGFβ1 gene Smad 4 gene IHC ISH
  • 相关文献

参考文献9

  • 1Edmondson HA, Steiner PE. Primary carcinoma of the liver - a study of 100 case among 48,900 nacropsies [J]. Cancer, 1954,7:462.
  • 2Fromowitz FB ,Viola MV ,Chao S, et al. Ras p21 expression in the progression of breast cancer[J]. Human Pathol, 1987,18 (12) :1268.
  • 3Wilentz Re, Su GH, Dai JL, et al. hnmunohistochemical labeling for DPCA mirrors geneticstatus in pancreaticadeno carcinomas : anewmarker of DPC4 in activation [J]. Am J Pathol, 2000,156:37.
  • 4Ijichi H. TGF-beta signaling pathway in pancreatic cancer cells [J]. Nippon Rinsho, 2004,62 (7) : 1241.
  • 5Baldus SE, Schwarz E, Lohrey C, et al. Smad 4 deficiency in cervical carcinoma cells [ J ]. Oncogene, 2005,24 ( 5 ) : 810.
  • 6Yakicier MC,Irmak MB, Romano A, et al. Smad 2 and Smad 4 gene mutations in hepatocellular carcinoma [J]. Oncogene, 1999,18 (34) :4879.
  • 7刘政,季国忠,缪林,杨春,张平.人肝癌及癌旁组织中Smad4、Smad7mRNA和蛋白表达研究[J].天津医药,2004,32(12):721-723. 被引量:13
  • 8Pardali K, Kowanetz M, Heldin CH, et al. Smad pathway-specific transcriptional regulation of the cell cycle inhibitor p21 ( WAF1/Cipl ) [J]. J Cell Physiol,2005, 182 (2) :205.
  • 9吴晓玲,曾维政,蒋明德,王丕龙,邓桂英,秦建平.红景天甙对肝纤维化大鼠Samds基因表达的影响[J].第四军医大学学报,2005,26(10):923-926. 被引量:29

二级参考文献12

  • 1Gressner AM,Weiskirchen R,Breitkopf K,et al.Roles of TGF-beta in hepatic fibrosis[J].Front Biosci,2002;7:d793-d807.
  • 2Liu CH,Marianna DA,Gaca E,et al.Smads 2 and 3 are differentially activated by transforming growth factor-β (TGF-β) in quiescent and activated hepatic stellate cells[J].J Biol Chem,2003;278(13):11721-11728.
  • 3Kondou H,Mushiake S,Etani Y,et al.A blocking peptide for transforming growth factor-beta 1 activation prevents hepatic fibrosis in vivo[J].J Hepatol,2003;39(5):742-748.
  • 4Dooley S,Hamzavi J,Breitkopf K,et al.Smad 7 prevents activation of hepatic stellate cells and liver fibrosis in rats[J].Gastroenterology,2003;125(1):178-191.
  • 5Villanueva A, Garcia C, Paules AB, et al. Disruption on the antiprolif erative TGF-beta signaling pathway in human pancreatic cancer cells. Oncogene, 1998,17(15): 1969 - 1978
  • 6Xu J, Attisano L. Mutations in the tumor suppressors Smad 2 and Smad 4 inactivate transforming growth factor beta signaling by targeting mads to the ubiquitin-proteasome pathway. Proc Natl Acad Sci USA, 2000, 97 (9) :4820 - 4825
  • 7Torbenson M, Marinopoulos S, Dang DT, et al. Smad 4 overexpression in hepatocellular carcinoma is strongly associated with transforming growth factor beta Ⅱ receptor immunolabeling. Hum Pathol, 2002,33 (9): 871- 876
  • 8KleeffJ, IshiwataT, MaruyamaH, et al. The TGF-beta signaling inhib itor Smad 7 enhances tumorigenicity in pancreatic cancer. Oncogene,1999,18(39) :5363 - 5372
  • 9Kawate S, Ohwada S, Hamada K, et al. Mutational analysis of the Smad 6 and Smad 7 genes in hepatocellular carcinoma. Int J MoL Med, 2001, 8(1):49-52
  • 10Schwarte-Waldhoff I, Volpert OV, Bouck NP, et al. Smad 4/DPCA-medi ated tumor suppression through suppression of angiogenesis, Proc Natl Acad SCi USA, 2000,97(17) :9624-9629

共引文献38

同被引文献9

  • 1耿呈云,薛新波.TGF-β1、Smad7在甲状腺癌中的表达和意义[J].临床外科杂志,2006,14(3):145-146. 被引量:6
  • 2Strick R,Ackermann S,Langbein M et al.Proliferation and cell-cell fusion of endometrial carcinoma are induced by the human endogenous retroviral syncytin-1 and regulated by TGF-beta(J).J Mol Med(Berl),2007,85(1):23.
  • 3Komiyama S,Kurahashi T,Ishikawa M et al.Expression of TGFβ1 and its receptors is associated with biological features of ovarian cancer and sensitivity to paclitaxel/carboplatin(J).Oncol Rep,2011,25(4):1131.
  • 4Liu FS,Chen JT,Hsieh YT et al.Loss of Smad4 protein ex-pression occurs infrequently in endometrial carcinomas(J).Int J Gynecol Pathol,2003,22(4):347.
  • 5Nikolic A,Ristanovic M,Perovic V et al.Genetic alterations in SMAD4 and K-ras in Serbian patients with endometrial carci-noma(J).Int J Gynecol Cancer,2012,22(3):442.
  • 6D'Inzeo S,Nicolussi A,Donini CF et al.A novel human Smad4 mutation is involved in papillary thyroid carcinoma pro-gression(J).Endocr Relat Cancer,2012,19(1):39.
  • 7Piestrzeniewicz-Ulanska D,Brys M,Semczuk A et al.TGF-beta signaling is disrupted in endometrioid-type endometrial carcinomas(J).Gynecol Oncol,2004,95(1):173.
  • 8庞久玲,马征,刘军,刘爱东.Smad3和转化生长因子β1在瘢痕疙瘩、增生性瘢痕及正常皮肤中的表达:48∶40∶40例标本病理检测[J].中国组织工程研究与临床康复,2010,14(11):1927-1930. 被引量:29
  • 9庞久玲,刘爱东,刘军.转化生长因子β1和基质金属蛋白酶在病理性瘢痕中的表达及意义[J].实用医学杂志,2010,26(17):3175-3177. 被引量:29

引证文献1

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