ERK1、ERK2及磷酸化的ERK1/2在结直肠癌中的表达及临床意义
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摘要
目的:检测ERK 1、ERK 2及p-ERK 1/2在结直肠癌中的表达,探讨其表达水平与临床指标的相关性。方法:收集2014-09~2016-09在我院因结直肠腺癌行手术治疗的120例病人的癌组织及癌旁组织,通过q PCR检测ERK 1、ERK 2在癌和癌旁组织中的表达,通过IHC、Western blot检测ERK 1、ERK 2及p-ERK 1/2蛋白的表达,分析其与临床指标的相关性。结果:与癌旁组织相比,ERK 1、ERK 2 mRNA在癌组织中显著高表达,且与癌组织的分化程度相关。Western Blot显示ERK 1、ERK 2及p-ERK 1/2蛋白在癌组织中均高表达。免疫组化显示ERK 1、ERK 2和p-ERK 1/2在癌组织中的阳性率分别为85.0%、79.2%和81.7%,显著高于癌旁组织(分别为8.3%、10.8%和11.7%)。癌细胞分化越差、TNM分期越高以及有淋巴结转移者,其ERK 1,ERK 2及pERK 1/2的蛋白表达量越高。结论:ERK 1、ERK 2及p-ERK 1/2在结直肠癌中显著高表达,与肿瘤的分化程度、淋巴结转移和TNM分期密切相关。ERK 1/2和p-ERK 1/2有望成为结直肠癌靶向治疗的关键靶点。
Objective: To explore the expression and clinical pathological significances of ERKl,ERK 2 and p-ERK 1/2 by detecting expression of them in colorectal cancer tissues.Methods: 120 cases of human colorectal cancer tissues and adjacent tumor tissues were collected in our hospital from2014-09 to 2016-09.The mRNA expression level was detected using reverse transcription PCR while protein level was detected by Western blotting and immunohistochemistry( IHC),respectively. The correlations between the protein level and clinical pathological significances were analyzed. Results: Compared with colorectal mucosa tissues,the mRNA expression of ERKl and ERK 2 in cancer tissues were significantly increased,respectively,and related to the level of tumor differentiation.The protein level of ERK 1,ERK 2 and p-ERK 1/2 showed by western blot were also significantly increased in cancer tissues.The positive rate of ERK 1,ERK 2 and p-ERK decided by IHC in cancer tissues were 85.0%、79.2% and 81.7%,significantly higher than adjacent tumor tissues,respectively. The high expression of these three proteins was significant correlation with the poor differentiation,high TNM staging,and lymphatic metastasis.Conclusion: The significantly increased expression of ERKl,ERK 2 and p-ERK 1/2 in colonic and rectal cancer tissues are significantly related to differentiation of tumor cell,lymphatic metastasis and clinical stage.ERK 1/2 and p-ERK 2 may become potential therapeutic targets for the treatment of colorectal cancer.
Objective: To explore the expression and clinical pathological significances of ERKl,ERK 2 and p-ERK 1/2 by detecting expression of them in colorectal cancer tissues.Methods: 120 cases of human colorectal cancer tissues and adjacent tumor tissues were collected in our hospital from2014-09 to 2016-09.The mRNA expression level was detected using reverse transcription PCR while protein level was detected by Western blotting and immunohistochemistry( IHC),respectively. The correlations between the protein level and clinical pathological significances were analyzed. Results: Compared with colorectal mucosa tissues,the mRNA expression of ERKl and ERK 2 in cancer tissues were significantly increased,respectively,and related to the level of tumor differentiation.The protein level of ERK 1,ERK 2 and p-ERK 1/2 showed by western blot were also significantly increased in cancer tissues.The positive rate of ERK 1,ERK 2 and p-ERK decided by IHC in cancer tissues were 85.0%、79.2% and 81.7%,significantly higher than adjacent tumor tissues,respectively. The high expression of these three proteins was significant correlation with the poor differentiation,high TNM staging,and lymphatic metastasis.Conclusion: The significantly increased expression of ERKl,ERK 2 and p-ERK 1/2 in colonic and rectal cancer tissues are significantly related to differentiation of tumor cell,lymphatic metastasis and clinical stage.ERK 1/2 and p-ERK 2 may become potential therapeutic targets for the treatment of colorectal cancer.
引文
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[13]乌日尼勒图,德力格尔图,刘暘.Cox-2和mmp-2在结直肠癌浸润转移中的表达及意义[J].内蒙古医科大学学报,2015;37(3):232-237
[14]Wang Q,Tang H,Yin S,et al.Downregulation of microRNA-138enhances the proliferation,Migration and invasion of cholangiocarcinoma cells through the upregulation of rhoc/p-erk/mmp-2/mmp-9[J].Oncol Rep,2013;29(5):2046-2052
[15]Ding C,Luo J,Li L,et al.Gab 2 facilitates epithelial-tomesenchymal transition via the mek/erk/mmp signaling in colorectal cancer[J].J Exp Clin Cancer Res,2016;35(3):5
[2]Zhang X,Ma L,Qi J,et al.Mapk/erk signaling pathwayinduced hyper-O-glcnacylation enhances cancer malignancy[J].Mol Cell Biochem,2015;410(1/2):101-110
[3]Cursons J,Gao J,Hurley DG,et al.Regulation of erk-mapk signaling in human epidermis[J].BMC Syst Biol,2015;9(1):41
[4]Lu R,Wu S,Zhang YG,et al.Salmonella protein avra activates the stat 3 signaling pathway in colon cancer[J].Neoplasia,2016;18(5):307-316
[5]Nussinov R,Tsai CJ,Jang HO,et al.Ncogenic kras signaling and yap1/β-catenin:similar cell cycle control in tumor initiation[J].Semin Cell Dev Biol,2016;58(4):79-85
[6]Sun WJ,Huang H,He B,et al.Romidepsin induces G2/M phase arrest via erk/cdc 25 C/cdc2/cyclinb pathway and apoptosis induction through jnk/C-jun/caspase 3 pathway in hepatocellular carcinoma cells[J].Biochem Pharmacol,2017;127(2):90-100
[7]Hu L,Xia L,Zhou H,et al.TF/fviia/par 2 promotes cell proliferation and migration via pkcαand erk-dependent C-jun/AP-1pathway in colon cancer cell line SW620[J].Tumour Biol,2013;34(5):2573-2581
[8]Tischlerova V,Kello M,Budovska M,et al.Indole phytoalexin derivatives induce mitochondrial-mediated apoptosis in human colorectal carcinoma cells[J].World J Gastroenterol,2017;23(24):4341-4353
[9]Nishinaka T,Miura T,Sakou M,et al.Down-regulation of aldo-keto reductase akr 1 B10gene expression by a phorbol ester via the erk/C-jun signaling pathway[J].Chem Biol Interact,2015;234(4):274-281
[10]李印,周清华,孙芝琳,等.靶向抑制erk1/2信号传导通路对人高转移大细胞肺癌细胞株L9981恶性表型的影响[J].中国肺癌杂志,2005;6(8):504-509
[11]Gysin S,Lee SH,Dean NM,et al.Pharmacologic inhibition of raf/mek/erk signaling elicits pancreatic cancer cell cycle arrest through induced expression of p 27 kip1[J].Cancer Res,2005;65(11):4870-4880
[12]Nishihara H,Hwang M,Kizaka-kondoh S,et al.Cyclic amp promotes camp-responsive element-binding proteindependent induction of cellular inhibitor of apoptosis protein-2and suppresses apoptosis of colon cancer cells through erk1/2and p 38 mapk[J].J Biol Chem,2004;279(25):26176-26183
[13]乌日尼勒图,德力格尔图,刘暘.Cox-2和mmp-2在结直肠癌浸润转移中的表达及意义[J].内蒙古医科大学学报,2015;37(3):232-237
[14]Wang Q,Tang H,Yin S,et al.Downregulation of microRNA-138enhances the proliferation,Migration and invasion of cholangiocarcinoma cells through the upregulation of rhoc/p-erk/mmp-2/mmp-9[J].Oncol Rep,2013;29(5):2046-2052
[15]Ding C,Luo J,Li L,et al.Gab 2 facilitates epithelial-tomesenchymal transition via the mek/erk/mmp signaling in colorectal cancer[J].J Exp Clin Cancer Res,2016;35(3):5