Comparative proteomic analysis reveals differentially expressed proteins regulated by a potential tumor promoter, BRE, in human esophageal carcinoma cells

Abstract

Esophageal tumorigenesis is a complex and cascading process, involving the interaction of many genes and proteins. In this study, we have used the comparative proteomic approach to identify tumor-associated proteins and explore the carcinogenic mechanisms. Two-dimensional electrophoresis (2-DE) and MALDI-TOF MS analysis of esophageal carcinoma and control cells revealed 10 proteins that were upregulated. A further 10 proteins were downregulated. Among these 20 differentially expressed proteins, brain and reproductive organ-expressed (BRE) protein was identified as a potential tumor promoter. It was high expressed by the esophageal carcinoma cells, as confirmed by RT-PCR and immunoblotting. BRE has been reported to be a stress-responsive protein. To gain further insight into its function, BRE expression was silenced in esophageal carcinoma cells using BRE-specific small interference RNA. It was discovered that silencing BRE expression downregulated prohibitin expression, but upregulated tumor-suppressor p53 expression. Furthermore, cyclin A and CDK2 expressions were suppressed suggesting that BRE inhibited cell proliferation. These results implied that BRE plays a significant role in mediating antiapoptotic and proliferative responses in esophageal carcinoma cells.

High BRE expression predicts favorable outcome in adult acute myeloid leukemia, in particular among MLL-AF9–positive patients

“…29,30 BRE also down regulates TNF␣ signaling by binding death receptors 31 and overexpression of BRE inhibits apoptosis. [31][32][33] Differentially high BRE expression occurred in 3% of the AML patients, while the remaining patients showed only small differences in BRE expression. No high BRE expression was found in donor CD34 ϩ cells, total BM or several mature blood cells, nor in several t(9;11) cell lines tested by us (supplemental Figure 3) or others.…”

High BRE expression in pediatric MLL-rearranged AML is associated with favorable outcome

“…15,35 Recently, overexpression of BRE has been described in hepatocellular and esophageal carcinomas. 32,36 However, to date BRE has never been associated with hematological malignancies. This study shows that BRE has a role in pediatric AML and mainly in patients with t(9;11)(p22;q23).…”

Current advances in esophageal cancer proteomics

“…To explore carcinogenic mechanisms through protein profiling, Chen et al examined soluble proteins differentially expressed in EC and non-cancerous cells using 2-DE and MALDI-TOF MS [80]. Among 20 differentially expressed protein spots, brain and reproductive organ-expressed (BRE) protein was selected and functionally analyzed using small interference RNA (Table 2).…”