哈萨克族食管癌患者中Lrig1通过MEK-ERK信号通路调控NF-κB及MMP-2表达*

摘要

目的：探讨Lrig1、NF-κB及MMP-2在哈萨克族食管癌患者中的表达与PI3K-AKT、MEK-ERK信号通路及与临床病理指标之间的关系。方法：采用RT-PCR方法检测48例哈萨克族食管癌患者组织中Lrig1、NF-κB、MMP-2表达，探讨NF-κB、MMP-2的表达与Lrig1的关系。纳入PI3K及MEK信号通路的关键基因PI3K、AKT1、MEK1、MEK2、MEK5、ERK1、ERK2，研究Lrig1调控NF-κB、MMP-2基因表达的通路。结果：转录水平mRNA检测显示在肿瘤组织及远端正常组织中NF-κB（P<0.001，P=0.014）、MMP-2（P=0.003，P=0.045）的表达与Lrig1 mRNA表达相关；蛋白水平Western blot检测显示Lrig1与NF-κB、MMP-2可能呈负相关。在肿瘤组织中MEK5（P<0.001）及ERK2（P=0.009）的表达与Lrig1相关；PI3K在正常组织中（P<0.001）的表达与Lrig1相关。Lrig1、MMP-2及NF-κB协同表达率为52.1%（25/48），其协同表达与淋巴结转移相关（P=0.020）。结论：NF-κB、MMP-2与Lrig1协同表达促进食管癌患者的淋巴结转移，Lrig1可能是通过MEK-ERK信号通路调控相关基因表达。%This work aimed to investigate the expression levels of Lrig1, NF-κB, and MMP-2 in Hazak's esophageal squamous cell carcinoma (ESCC), as well as to explore the relationship of Lrig1 expression through the PI3K-AKT and MEK-ERK signaling pathways with clinicopathological indices. Methods:First, RT-PCR analysis was performed to study the expression levels of Lrig1, NF-κB, and MMP-2 in 48 ESCC and noncancerous specimens. Second, some key genes of the PI3K and MEK signaling pathways such as PI3K, AKT1, MEK1, MEK2, MEK5, ERK1, and ERK2 were detected in Lrig1-positive and-negative tissues to identify the possible signaling pathway of Lrig1-regulated NF-κB and MMP-2 expression. Results:The expression of NF-κB (P<0.001, P=0.014) and MMP-2 (P=0.003, P=0.045) was significantly correlated with Lrig1 in cancer and distal normal tissues. Lrig1 may be negatively correlated with NF-κB and MMP-2 at the protein level. MEK5 (P<0.001) and ERK2 (P=0.009) expression was associated with Lrig1 in cancer tissues. PI3K expression was correlated with Lrig1 in the distal normal tissues (P<0.001). The coordinate expression ratio of Lrig1 to NF-κB and MMP2 reached 52.1%(25/48). This co-expression may be related to lymph node metastasis (P=0.020) but not to other clinicopathological features. Conclusions:These findings suggest that MMP-2 and NF-κB expression is related to Lrig1 in Hazak's ESCC, and that MEK and ERK2 mRNA expression are related to Lrig1. The co-expression of NF-κB, MMP-2, and Lrig1 may promote lymph node metastasis in ESCC among Hazak people. Lrig1 may regulate the expression of target genes not through the PI3K-AKT pathway but through the MEK-ERK signaling pathway. Further related studies are needed in the future.