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Abstract
BackgroundBy using cDNA microarray analysis, we identified a G protein-coupled receptor, GPR39, that is significantly up-regulated in ESCC. The aim of this study is to investigate the role of GPR39 in human esophageal cancer development, and to examine the prevalence and clinical significance of GPR39 overexpression in ESCC.MethodsThe mRNA expression level of GPR39 was analyzed in 9 ESCC cell lines and 50 primary ESCC tumors using semi-quantitative RT-PCR. Immunohistochemistry was used to assess GPR39 protein expression in tissue arrays containing 300 primary ESCC cases. In vitro and in vivo studies were done to elucidate the tumorigenic role of GPR39 in ESCC cells.ResultsWe found that GPR39 was frequently overexpressed in primary ESCCs in both mRNA level (27/50, 54%) and protein level (121/207, 58.5%), which was significantly associated with the lymph node metastasis and advanced TNM stage (P < 0.01). Functional studies showed that GPR39 has a strong tumorigenic ability. Introduction of GPR39 gene into ESCC cell line KYSE30 could promote cell proliferation, increase foci formation, colony formation in soft agar, and tumor formation in nude mice. The mechanism by which amplified GPR39 induces tumorigenesis was associated with its role in promoting G1/S transition via up-regulation of cyclin D1 and CDK6. Further study found GPR39 could enhance cell motility and invasiveness by inducing EMT and remodeling cytoskeleton. Moreover, depletion of endogenous GPR39 by siRNA could effectively decrease the oncogenicity of ESCC cells.ConclusionsThe present study suggests that GPR39 plays an important tumorigenic role in the development and progression of ESCC.
Highlights
By using cDNA microarray analysis, we identified a G protein-coupled receptor, GPR39, that is significantly up-regulated in Esophageal squamous cell carcinoma (ESCC)
GPR39 is frequently overexpressed in ESCC Semi-quantitative RT-PCR was used to study the expression status of GPR39 in 50 primary ESCCs and 9 ESCC cell lines
Overexpression of GPR39 was frequently detected in ESCC cell lines (HKESC1, KYSE140, KYSE180, KYSE410, KYSE510 and KYSE520; Figure 1B)
Summary
By using cDNA microarray analysis, we identified a G protein-coupled receptor, GPR39, that is significantly up-regulated in ESCC. The aim of this study is to investigate the role of GPR39 in human esophageal cancer development, and to examine the prevalence and clinical significance of GPR39 overexpression in ESCC. GPR39 belongs to the G protein-coupled receptors (GPCRs) superfamily, which is the largest family of cell-surface molecules involved in signal transmission. GPR39 receptor is thought to be activated by Zn2+ signals and may have other, as yet unidentified, cognitive ligands [9]. Emerging evidence indicates that G protein-coupled receptors are crucial players in cancer progression and metastasis [13,14], the role of GPR39 in cancer development remains unclear. The clinical significance of GPR39 overexpression in ESCC was investigated
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