胃癌组织中ADD1、Ptch1、Gli1表达观察
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摘要
目的观察胃癌组织中细胞膜骨架蛋白α-Adducin(ADD1)及Hedgehog(Hh)信号通路分子跨膜蛋白Patched1(Ptch1)、转录因子Gli1的表达变化,并分析其相关性。方法行手术治疗的胃癌患者60例,术中留取胃癌组织和癌旁正常胃组织各60例。采用Western blotting法检测胃癌组织及正常胃组织中的ADD1、Ptch1、Gli1蛋白,采用real-time PCR法检测ADD1、Ptch1、Gli1 mRNA。分析ADD1、Ptch1、Gli1蛋白及mRNA表达与胃癌临床病理参数的关系,分析胃癌组织中ADD1、Ptch1、Gli1蛋白及mRNA表达的相关性。结果胃癌组织中ADD1、Ptch1、Gli1蛋白及mRNA相对表达量均高于正常胃组织(P均<0.05)。低分化、Ⅲ~Ⅳ期、有浆膜浸润、有淋巴结转移的胃癌组织中ADD1、Ptch1、Gli1蛋白及mRNA表达分别高于高分化、Ⅰ~Ⅱ期、无浆膜浸润、无淋巴结转移的胃癌组织(P均<0.05)。胃癌组织中ADD1蛋白与Ptch1蛋白、Gli1蛋白表达均呈正相关关系(r分别为0.759、0.681,P均<0.01),ADD1 mRNA与Ptch1 mRNA、Gli1 mRNA表达也呈正相关关系(r分别为0.811、0.719,P均<0.01)。结论胃癌组织中ADD1、Ptch1、Gli1蛋白及mRNA呈高表达,ADD1、Ptch1、Gli1可能共同参与胃癌的发生发展,且ADD1与Hh信号通路之间可能存在一定相互作用关系。
引文
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[17]Shen N,Liu C,Li J,et al.A Phosphorylation-Related Variant ADD1-rs4963 Modifies the Risk of Colorectal Cancer[J].PLo S One,2015,10(3):e0121485.
[18]Jen J,Lin LL,Chen HT,et al.Oncoprotein ZNF322A transcriptionally deregulates alpha-adducin,cyclin D1 and p53 to promote tumor growth and metastasis in lung cancer[J].Oncogene,2016,35(18):2357-2369.
[2]Lee SJ,Do IG,Lee J,et al.Gastric cancer(GC)patients with hedgehog pathway activation:PTCH1 and GLI2 as independent prognostic factors[J].Target Oncol,2013,8(4):47-58.
[3]Ma XL,Sun HJ,Wang YS,et al.Study of Sonic hedgehog signaling pathway related molecules in gastric carcinoma[J].World J Gastroenterol,2006,12(25):3965-3969.
[4]Yoo YA,Kang MH,Kim JS,et al.Sonic hedgehog signaling promotes motility and invasiveness of gastric cancer cells through TGFbeta-mediated activation of the ALK5-Smad3 pathway[J].Carcinogenesis,2008,29(3):480-490.
[5]Harris LG,Samant RS,Shevde LA.Hedgehog signaling:networking to nurture a promalignant tumor microenviroment[J].Mol Cancer Res,2011,9(9):1165-1174.
[6]Yan Y,Wang LF,Wang RF.Role of cancer-associated fibroblasts in invasion and metastasis of gastric cancer[J].World J Gastroenterol,2015,21(33):9717-9726.
[7]Atwood SX,Sarin KY,Whitson RJ,et al.Smoothened variants explain the majority of drug resistance in Basal cell carcinoma[J].Cancer Cell,2015,27(3):342-353.
[8]Sharpe HJ,Pau G,Dijkgraaf GJ,et al.Genomic analysis of smoothened inhibitor resistance in Basal cell carcinoma[J].Cancer Cell,2015,27(3):327-341.
[9]Di Magno L,Coni S,Di Marcotullio L,et al.Digging a hole under Hedgehog:downstream inhibition as an emerging anticancer strategy[J].Biochim Biophys Acta,2015,1856(1):62-72.
[10]Infante P,Alfonsi R,Botta B,et al.Targeting GLI factors to inhibit the Hedgehog pathway[J].Trends Pharmacol Sci,2015,36(8):547-558.
[11]Pandolfi S,Stecca B.Cooperative integration between HEDGEHOG-GLI signalling and other oncogenic pathways:implications for cancer therapy[J].Expert Rev Mol Med,2013,80(9):734-743.
[12]Ramalho-Santos M,Melton DA,Mc Mahon AP.Hedgehog signals regulate multiple aspects of gastrointestinal development[J].Development,2000,127(12):2763-2772.
[13]李东伟,刘宏斌,曹廷宝,等.音猬因子、Ptch1基因在胃癌中的表达及临床意义[J].现代肿瘤医学,2015,23(18):2620-2624.
[14]Fernandez-Zapico ME.GLI1 finds a new role in cancer stem cell biology[J].EMBO Mol Med,2013,5(4):483-485.
[15]Li SH,Fu J,Watkins DN,et al.Sulforaphane regulates self-renewal of pancreatic cancer stem cells through the modulation of Sonic Hedgehog-Gli1 pathway[J].Mol Cell Biochem,2013,373(1-2):217-227.
[16]刘道永,邓军,郭伟,等.Gli-1蛋白在胃癌中的表达及临床意义[J].中华全科医学,2013,11(9):1342-1343.
[17]Shen N,Liu C,Li J,et al.A Phosphorylation-Related Variant ADD1-rs4963 Modifies the Risk of Colorectal Cancer[J].PLo S One,2015,10(3):e0121485.
[18]Jen J,Lin LL,Chen HT,et al.Oncoprotein ZNF322A transcriptionally deregulates alpha-adducin,cyclin D1 and p53 to promote tumor growth and metastasis in lung cancer[J].Oncogene,2016,35(18):2357-2369.