Initiation of malignancy by duodenal contents reflux and the role of ezrin in developing esophageal squamous cell carcinoma
Abstract
Gastroesophageal reflux has recently been implicated as a causative factor in upper aerodigestive tract carcinogenesis. Esophageal squamous cell carcinomas (ESCCs) have developed in duodenal-content reflux animals without any known carcinogen present. We established a cell line, designated ESCC-DR, from a thoracic metastatic tumor in a reflux animal. To gain insight into the genomic alterations associated with duodenal content reflux-induced carcinogenesis, we first performed comparative genomic hybridization using an Agilent rat 244K array in ESCC-DR and identified many chromosomal gains and losses. Of the many genes identified, we detected an interesting ezrin amplicon that has been recently reported in human ESCC. Ezrin, which cross-links the cytoskeleton and plasma membrane, is involved in the growth and metastatic potential of cancer cells. Overexpression of ezrin protein in ESCC-DR was confirmed by Western blotting. We also compared ezrin protein expression levels and patterns in hyperplastic, dysplastic, ESCC, and metastatic sites developed in two distinct reflux models using immunohistochemistry. Immunohistochemical staining of ezrin revealed overexpression in the nucleus, and the cytoplasm as well as plasma membrane of...Continue Reading
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