OE33 was derived from an esophageal adenocarcinoma and is maintained by The European Collection of Cell Cultures (Sigma-Aldrich, Corp. When SELENBP1 expression was reconstituted in vitro, tumor cells responded to selenium treatment with increased apoptosis, increased cellular senescence and increased sensitivity to cisplatin.įlo-1 was derived from a patient with esophageal adenocarcinoma and has been described previously ( 17). Decreased expression appeared to be regulated both by methylation of the SELENBP1 promoter and by alternative splicing of SELENBP1 mRNA. We observed that SELENBP1 expression was decreased in primary esophageal adenocarcinoma tumor samples.
Although clear discrepancies were observed between the levels of mRNA and protein expression, mouse selenium-binding proteins were found to be associated with the aging process in senescence-accelerated mouse models ( 16).īased on such findings, we evaluated the role of SELENBP1 in the tumorigenesis of esophageal adenocarcinoma as well as the impact of differential SELENBP1 expression and selenium supplementation on cell viability and chemosensitivity. While higher SELENBP1 expression has been shown to be associated with normal colonic epithelial differentiation ( 12), lower expression was associated with poor tumor differentiation in lung adenocarcinomas ( 9).
Higher levels of SELENBP1 expression in non-growing versus rapidly growing cells have been reported in both mouse and human cells ( 8, 15). Previous studies have reported a correlation between decreased expression of a chromosome 1q21 gene cluster and resistance to preoperative esophageal adenocarcinoma chemoradiotherapy ( 14). Its expression has been shown to be reduced markedly in multiple tumor types as compared to their corresponding normal tissues and its reduction has been associated with poor outcome in lung cancer ( 9), ovarian cancer ( 10), colorectal cancer ( 11, 12) and pleural mesothelioma ( 13). Selenium binding protein 1 (Chr:1q21 SBP1, SELENBP1, hSP56) has been shown to bind selenium covalently ( 5, 6) and is expressed in a variety of tissues and cell lines ( 7, 8).
Organic selenium compounds such as methylseleninic acid appear to enhance response to chemotherapeutic agents such as cisplatin and paclitaxel possibly by down-regulation of antiapoptotic signals ( 3, 4). Serum selenium deficiency, in particular, has been associated with esophageal adenocarcinoma (EAC) as well as its precursor lesion, dysplastic Barrett's esophagus ( 2). Despite advances in endoscopic surveillance programs, surgical therapy and multimodality treatment, the prognosis of patients with EAC remains poor, with an overall 5-year survival of 5-12% ( 1). Esophageal adenocarcinoma (EAC) is increasing in incidence in Western countries and remains a highly lethal malignancy.
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