ERK expression and its correlation with STAT1 in esophageal squamous cell carcinoma.

Hu Wang,Hailong Yun,Shubiao Chen,Zhaoyong Liu,Yelong Chen,Ying Zhang

doi:10.18632/oncotarget.16902

Abstract

BackgroundEsophageal squamous cell carcinoma is one of leading causes of cancer-related deaths in Chaoshan region a high-risk region for esophageal cancer. Extracellular regulated protein kinases (ERK) usually play an important role in cell proliferation and differentiation. However, accumulating evidence has shown that the ERK was aberrantly expressed in cancers and correlated with STAT1 depression.ResultsThe activated ERK downregulates STAT1 expression in ESCC cell lines and U0126 increases expression of STAT1. Our immunohistochemistry result also confirms that the expression of ERK inversely correlated with that of STAT1 in ESCC tumors. In addition, a significantly higher expression of ERK/p-ERK was found in ESCC tissues in comparison with case-matched normal esophageal tissues (p < 0.05). Moreover, the immunohistochemical analysis demonstrated that ERK expression was paralleled with the differentiation and clinical stage. In 74 patients with follow-up data, those with ERKlow tumors survived significantly longer than those with ERKhigh tumors (p = 0.04); patients with ERKlow/STAT1high tumors had the longest survival (p = 0.001).Materials and MethodsTo investigate whether ERK can mediated STAT1 expression in ESCC, we used the MEK plasmid and U0126, a MEK inhibitor, to treat the cell. To further confirm our in-vitro study, we detected the ERK, p-ERK and STAT1 expression in 131 ESCC cases and 22 case-matched normal esophageal tissues adjacent to the tumors specimens.ConclusionsThese findings provide pathological evidence that ERK/p-ERK is negatively correlated with STAT1 in ESCC. Our data suggests that inhibition of ERK and/or restoration of STAT1 expression maybe useful therapeutic strategies for ESCC.

Highlights

The mitogen-activated protein kinase (MAPK)extracellular regulated protein kinases (ERK) signaling pathway is a major regulator in a wide range of cellular processes such as cell proliferation, differentiation, survival and motility [1]
Our immunohistochemistry result confirms that the expression of Extracellular regulated protein kinases (ERK) inversely correlated with that of STAT1 in Esophageal squamous cell carcinoma (ESCC) tumors
To further confirm our in-vitro study, we detected the ERK, p-ERK and STAT1 expression in 131 ESCC cases and 22 case-matched normal esophageal tissues adjacent to the tumors specimens. These findings provide pathological evidence that ERK/p-ERK is negatively correlated with STAT1 in ESCC

Summary

Introduction

The mitogen-activated protein kinase (MAPK)extracellular regulated protein kinases (ERK) signaling pathway is a major regulator in a wide range of cellular processes such as cell proliferation, differentiation, survival and motility [1]. STATs become phosphorylated by specific receptor kinases, and activated STATs subsequently dimerize and translocate into the nucleus where they regulate gene expression [3]. STAT1 can be phosphorylated at serine 727 (S727) in response to different stimuli or activators, including ERK, IFNγ, lipopolysaccharide and ultraviolet irradiation [5,6,7]. Extracellular regulated protein kinases (ERK) usually play an important role in cell proliferation and differentiation. Accumulating evidence has shown that the ERK was aberrantly expressed in cancers and correlated with STAT1 depression

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