Characterization of a novel tumor suppressor gene UPK1A in esophageal squanous cell carcinoma

Abstract

Background: Esophageal Squamous Cell Carcinoma (ESCC) has been ranked as the sixth leading cause of cancer death over the world. Like other types of cancer, genetic variation in multiple cancer-related genes is one of the main causes of ESCC. Hence, to have a better understanding of ESCC, it is important to identify these key genes and recognize their roles. Recently, our group performed an Affemetrix cDNA Microarray comparing differentially expressed genes between ESCC tumors and their adjacent nontumorous tissues. Uroplakin 1a (UPK1A) was found to be down-regulated. In this study, the role UPK1A gene in ESCC was characterized. Methods and Results: By reverse transcription-polymerase chain reaction (RT-PCR), 43/50 (86%) primary ESCCs and 8/9 (89%) ESCC cell lines were found no expression of UPK1A which was correlated with promoter hypermethylation. In addition, functional studies such as colony formation in soft agar, cell proliferation assay, foci formation and tumor formation in nude mice showed that UPK1A could suppress the tumorigenicity of ESCC cells in vitro and in vivo. Wound healing assay and cell adhesion assay also suggested that UPK1A inhibit cell mobility and increase cell adhesion ability respectively. Conclusion: Our study indicated that UPK1A has an important suppressive ability in the development and progression which maybe a novel tumor-suppressor gene in ESCC.