TGF-β1及Smad4在大肠癌组织中表达及意义.doc

TGF-β1及Smad4在大肠癌组织中表达及意义[摘要] 目的：探讨TGF-β1与Smad4在大肠癌组织中的表达及其与大肠癌发生发展的关系。方法：应用免疫组织化学SABC法检测67例大肠癌组织中TGF-β1与Smad4蛋白表达。并选择24例正常人大肠黏膜组织作为正常对照组。结果：大肠癌组织中TGF-β1蛋白的阳性表达率为67.2%，较正常对照组(4.2%)明显增高(P Smad4基因最早由Hahn等在胰腺癌中发现，又名DPC4(deleted in pancreatic carcinoma 4)基因。研究表明，它是一个抑癌基因，能抑制肿瘤细胞的生长[12]。本研究结果显示Smad4蛋白在大肠癌组织中的保留表达率明显低于正常黏膜组织，无转移的大肠癌组织中Smad4蛋白的阳性表达率明显高于有淋巴转移的癌组织，提示Smad4蛋白低表达可能与大肠癌的发生发展有关。这与文献报道[13]一致。 Smad4蛋白是TGF-β信号传导中的唯一公共个体，在TGF-β1的刺激下，Smad4参与诱导P15(Ink4B)转录，从而抑制肿瘤细胞的增殖[14]。本试验结果显示TGF-β1与Smad4在大肠癌组织中的表达呈负相关，提示二者在肿瘤的形成与发展过程中可能有协同作用，但其协同作用的详细机制仍需进一步研究。 [参考文献] [1]Wang SF, Lai LC. The rule of TGF-β in human carcers[J].Pathology,2001,33(1):85-92. [2]Kinugasa S, Abe S, Tachibana M, et al. Overexpression of transforming growth factor-β1 in scirrhous carcinoma of the stomach correlates with decreased survival[J]. Oncology,1998,55(6):582-587. [3]Itoh S, Itoh F, Goumans MJ, et al. Signaling of transforming growth factor-β family members through Smad proteins[J]. Eur J Biochem,2000, 267:6954-6967. [4]Fink SP, Swinler SE, Lutterbaugh JD. Transforming growth factor-beta-induced growth inhibition in a Smad4 mutant colon adenoma cell line [J]. Cancer Res,2001,61(1):256-260. [5]Müller N, Reinacher-Schick A, Baldus S, et al. Smad4 induces the tumor suppressor E-cadherin and P-cadherin in colon carcinoma cells [J]. Oncogene,2002,21(39):6049-6058. [6]Massague J. Transforming growth factor-beta family[J].Annu Rev Cell Biol,1990,6:597-691. [7]Roberts AB. TGF-beta signaling from receptors to the nucleus[J].Microbes Infect,1999,1(15):1265-1273. [8]Yamatoto M, Maehara Y, Sakaguchi Y, et al. Transforming growth factor-beta1 induces apoptosis in gastric cancer cells through a p53-independent pathway [J]. Cancer,1996,77(8):1628-1633. [9]Li F, Cao Y, Townsend CM, et al. TGF-beta signaling in colon cancer cells [J]. World J Surg,2005,29(3):306-311. [10]Cardillo MR, Yap E. TGF-β1 in colonic neoplasia: A genetic molecular and immunohisochemical study[J]. E