Differential expression of ANXA1 in benign human gastrointestinal tissues and cancers.

Yunshu Gao,Ying Chen,Jiejun Wang,Dongyun Xu,Guanzhen Yu

doi:10.1186/1471-2407-14-520

Abstract

BackgroundAnnexin-1 contributes to the pathological consequence and sequelae of most serious human diseases including cardiovascular disease and cancer. Although diverse roles in carcinogenesis have been postulated, its role in human gastrointestinal cancers still remains controversial.MethodsThe mRNA and protein expression profiles of ANXA1 were studied in human esophageal, gastric, pancreatic, colorectal, liver, and bile duct cancers using Real-Time PCR, western blotting, and immunohistochemistry. Gain/loss-of-function by pcDNA3.1-ANXA1 and ANXA1-shRNA was performed in gastric cancer cells.ResultsANXA1 was widely expressed in adult gastrointestinal tissue. All methods showed that ANXA1 was down-regulated in esophageal, gastric, and bile duct cancers, but up-regulated in pancreatic cancer. Forced ANXA1 expression in gastric cancer cells leads to cell growth inhibition and concomitantly modulates COX-2 expression. We confirm loss of ANXA1 and overexpression of COX-2 in clinical gastric cancer, suggesting that the anti-proliferative function of ANXA1 against COX-2 production might be lost.ConclusionsANXA1 expression is “tumor-specific” and might play a multifaceted role in cancer development and progression. ANXA1 was widely expressed in normal gastrointestinal epithelium, suggesting its role in the maintenance of cellular boundaries. Furthermore, ANXA1 regulates GC cell viability via the COX-2 pathway.

Highlights

Annexin-1 contributes to the pathological consequence and sequelae of most serious human diseases including cardiovascular disease and cancer
ANXA1 expression profile in non-cancerous human gastrointestinal tissues The quantitative ANXA1 mRNA expression profile was investigated in normal human gastrointestinal tissues using real-time RT-PCR
ANXA1 expression profile in human gastrointestinal carcinomas Since ANXA1 has been proved to contribute to the tumorigenesis of various human malignancies, we investigated six of the more frequently occurring tumor entities in human gastrointestinal system for ANXA1 expression to reveal its potential role as a diagnostic marker or as a therapeutic target

Summary

Introduction

Annexin-1 contributes to the pathological consequence and sequelae of most serious human diseases including cardiovascular disease and cancer. The annexin superfamily consists of 13 calcium or calcium and phospholipid binding proteins expressed in most eukaryotic cell types Despite their high biological and structural homology (40-60%), annexins have diverse functions in cellular activities including vesicle trafficking, cell division, apoptosis, calcium signaling, and growth regulation. The expression levels of annexins or their localization changed remarkably, which suggests that annexins may contribute to the pathological consequence and sequelae of most serious human diseases including cardiovascular disease and cancer [1]. More recently, ANXA1 protein has been recognized to be differentially expressed in various human tumors, e.g., breast cancer, prostate cancer, esophageal cancer, gastric cancer, endometrial carcinoma, pancreatic cancer, and colorectal cancer [2,3,4,5,6,7,8,9,10,11,12,13]. The importance of ANXA1 in cancer is apparent and antibodies for therapeutic invention were prepared, researchers and clinicians are hampered by the conflicting expression pattern of ANXA1 in human solid cancers and by the lack of complete data sets describing the tissuespecific expression of this gene/protein

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