摘要
目的:探究钙/钙调蛋白依赖性蛋白激酶Ⅱ(calcium/calmodulin-dependent protein kinaseⅡ,CaMKⅡ)在肺腺癌组织中的表达及其促进肺腺癌的侵袭、转移。方法:通过免疫组织化学染色(immunohistochemistry,IHC)分析肺腺癌患者的石蜡组织标本CaMKⅡ表达与临床病理参数关系,同时对肺腺癌组织与其配对淋巴结转移病灶中的CaMKⅡ表达情况进行比较分析,收集2011年1月至2011年12月于天津医科大学肿瘤医院行手术治疗的113例肺腺癌患者及21例配对的原发病灶及淋巴结转移病灶的石蜡组织标本。将肺腺癌细胞系H1299及Calu3进行慢病毒转染,实验组转染高表达CaMKⅡ病毒,对照组转染阴性对照病毒,通过Transwell实验和划痕实验检测肺腺癌细胞侵袭、转移能力,通过Western blot检测CaMKⅡ表达水平与上皮间充质转化(pithelial-mesenchymal transition,EMT)相关指标和表皮生长因子受体(epidermal growth factor receptor,EGFR)通路激活间的关系。结果:CaMKⅡ高表达与肺腺癌TNM分期和淋巴结转移呈正相关,肺腺癌淋巴结转移病灶中的癌组织CaMKⅡ表达明显高于其原发病灶(P<0.05)。细胞实验表明,CaMKⅡ高表达的肺腺癌细胞,其穿膜细胞数目明显增多,伤口愈合能力增强;EGFR通路激活后p-CaMKⅡ水平增加,且CaMKⅡ促进了EMT相关蛋白及转录因子的表达。结论:CaMKⅡ参与EGFR信号传导,促进EMT过程,增加肺腺癌的侵袭转移能力。
Objective:To investigate the expression of calcium/calmodulin-dependent protein kinase Ⅱ(CaMK Ⅱ) in lung adenocarcinoma and determine its role in lung adenocarcinoma invasion and metastasis.Methods:The relationship between the expression of CaMK Ⅱ and clinicopathological parameters of patients with lung adenocarcinoma was analyzed using immunohistochemistry(IHC) staining of paraffinembedded tissue sections.Concurrently,the expression of CaMK Ⅱ in lung adenocarcinoma and its paired lymph node metastases was compared,paraffin tissue samples from 113 patients with lung adenocarcinoma and 21 matched primary and lymph node metastases were collected from patients with lung adenocarcinoma who underwent surgical treatment in Tianjin Medical University Cancer Institute & Hospital from January to December 2011.The H1299 and Calu3 lung adenocarcinoma cell lines were transfected lentivirus with the high expression Ca MKⅡ vector in the experimental group and negative control vector in the control group.Invasion and metastasis of the lung adenocarcinoma cells were investigated using Transwell and scratch tests,respectively.The relationship between CaMK Ⅱ expression and epithelial–mesenchymal transformation(EMT) and the activation of the epidermal growth factor receptor(EGFR) pathway was detected using Western blot.Results:Clinicopathological analysis revealed that the expression of CaMK Ⅱ was positively correlated with TNM stage and lymph node metastasis of lung adenocarcinoma.The expression of CaMK Ⅱ in lung adenocarcinoma with lymph node metastasis was significantly higher than that in the primary tumor(P<0.05).In vitro experiments showed that the number of transmembrane lung adenocarcinoma cells with increased CaMK Ⅱ expression was significantly elevated and the wound healing ability was enhanced.The level of phosphorylated-Ca MKⅡ increased after the activation of the EGFR pathway,and CaMK Ⅱ promoted the expression of EMT-related proteins and transcription factors.Conclusions:Ca MKⅡ participates in
作者
任丹阳
刘昶煦
李玲妹
黄秋娟
齐丽莎
曹文枫
Danyang Ren;Changxu Liu;Lingmei Li;Qiujuan Huang;Lisha Qi;Wenfeng Cao(Department of Pathology,Tianjin Medical University Cancer Institute&Hospital,National Clinical Research Center for Cancer,Tianjin Key Laboratory of Cancer Prevention and Therapy,Tianjin’s Clinical Research Center for Cancer,Tianjin 300060,China)
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2022年第11期548-553,共6页
Chinese Journal of Clinical Oncology
基金
天津市卫生健康委员会科技课题项目(编号:ZC20193)资助。
关键词
CaMKⅡ
肺腺癌
侵袭转移
上皮间充质转化
calcium/calmodulin-dependent protein kinaseⅡ(CaMKⅡ)
lung adenocarcinoma
invasion and metastasis
epithelial–mesenchymal transformation(EMT)
