Decreased Selenium-Binding Protein 1 in Esophageal Adenocarcinoma Results from Posttranscriptional and Epigenetic Regulation and Affects Chemosensitivity

Abstract

Purpose: The chemopreventive effects of selenium have been extensively examined, but its role in cancer development or as a chemotherapeutic agent has only recently been explored. Because seleniumbinding protein 1 (SELENBP1, SBP1, hSP56) has been shown to bind selenium covalently and selenium deficiency has been associated with esophageal adenocarcinoma (EAC), we examined its role in EAC development and its potential effect on chemosensitivity in the presence of selenium. Experimental Design: SELENBP1 expression level and copy number variation were determined by oligonucleotide microarrays, real-time reverse transcription-PCR, tissue microarrays, immunoblotting, and single-nucleotide polymorphism arrays. Bisulfite sequencing and sequence analysis of reverse transcription-PCR-amplified products explored epigenetic and posttranscriptional regulation of SELENBP1 expression, respectively. WST-1 cell proliferation assays, senescence-associated β-galactosidase staining, immunoblotting, and flow cytometry were done to evaluate the biological significance of SELENBP1 overexpression in selenium-supplemented EAC cells.Results: SELENBP1 expression decreased significantly in Barrett's esophagus to adenocarcinoma progression. Both epigenetic and posttranscriptional mechanisms seemed to modulate SELENBP1 expression. Stable overexpression of SELENBP1 in methylseleninic acid-supplemented Flo-1 cells resulted in enhanced apoptosis, increased cellular senescence, and enhanced cisplatin cytotoxicity. Although inorganic sodium selenite similarly enhanced cisplatin cytotoxicity, these two forms of selenium elicited different cellular responses.Conclusions: SELENBP1 expression may be an important predictor of response to chemoprevention or chemosensitization with certain forms of selenium in esophageal tissues.

Decreased Selenium-Binding Protein 1 Enhances Glutathione Peroxidase 1 Activity and Downregulates HIF-1α to Promote Hepatocellular Carcinoma Invasiveness

“…This conclusion was supported by several previous studies, which investigated SBP1 and GPX1 separately (8,18,38). On the other hand, the poor responses of patients with HCC to chemotherapy might be due to low SBP1 expression and high GPX1 activity, thus increasing SBP1 expression and decreasing GPX1 activity could be a novel strategy for cancer treatment.…”

“…The cellular biochemistry of selenium is a complex system that involves the expression of a wide range of selenium-containing proteins (4)(5)(6). Of these proteins, a 56-kDa molecule termed selenium-binding protein 1 (SBP1) was found to be the possible mediator of selenium's anticancer functions (7,8). SBP1 is expressed in various cell types, including liver, heart, and kidney (2), and previous studies have established a solid connection between SBP1 and cancer.…”

Competitive Binding Between Id1 and E2F1 to Cdc20 Regulates E2F1 Degradation and Thymidylate Synthase Expression to Promote Esophageal Cancer Chemoresistance

“…15,16), colon cancer (17,18), hepatocellular carcinoma (HCC; ref. 19), lung cancer (20), and breast cancer (21,22), were downloaded from the GEO database (accession numbers GSE23400, GSE47404, GSE13898, GSE37203, GSE28000, GSE28722, GSE10141,…”

Sodium Selenite Inhibits Proliferation of Gastric Cancer Cells by Inducing SBP1 Expression

“…The human selenium-binding protein 1 (SBP1, SELENBP1 or hSP56) gene is located at chromosome position 1q21-22 and is the homologue of the mouse SP56 gene (Yang and Diamond 2013). SBP1 has been shown to bind selenium covalently and has been found to be the possible mediator of selenium's anticancer functions (Porat et al 2000;Silvers et al 2010;Huang et al 2012). Selenium supplementation causes the increase in SBP1 expression, which affects cell viability and chemosensitivity of esophageal adenocarcinoma cells (Silvers et al 2010).…”

“…SBP1 has been shown to bind selenium covalently and has been found to be the possible mediator of selenium's anticancer functions (Porat et al 2000;Silvers et al 2010;Huang et al 2012). Selenium supplementation causes the increase in SBP1 expression, which affects cell viability and chemosensitivity of esophageal adenocarcinoma cells (Silvers et al 2010). A large body of evidence has recently demonstrated the protective role of selenium against several major types of cancers including gastric cancer (Liu and Russell 2008;Lee et al 2011).…”