Rabbit Anti-Human SERCA3 (a.a. 101-200) Polyclonal antibody

Recent studies have shown that expression of Sarco(endo)plasmic Reticulum Ca2+-ATPase 2 (SERCA2) is decreased in oral cancer; whereas expression of SERCA3 is considerably decreased or absent in human colon, gastric, breast, and lung cancers. The ATP2A2 and ATP2A3 genes encode SERCA2 and SERCA3 isoforms, respectively. Promoter methylation on CpG islands was responsible for the repression of ATP2A2 gene in human oral cancer samples. On the other hand, histone deacetylase inhibitors (HDACi) up-regulate ATP2A3 expression in gastric, colon, and lung cancer cells in culture, however, the molecular mechanism is unknown. In this study, we investigate whether HDACi and DNA methylation regulate ATP2A2 and ATP2A3 expression in human breast cancer cell lines. Results show a marked induction of SERCA3a and panSERCA3 mRNA expression in human MCF-7 and MDA-MB-231 cells treated with sodium butyrate (NaB) or trichostatin A (TSA); whereas SERCA2b mRNA expression did not change significantly. ChIP assays show that NaB or TSA treatment of MDA-MB-231 cells increases H3K9 acetylation on ATP2A3 promoter. NaB also decreases H3K9 trimethylation; suggesting that these modifications stimulate ATP2A3 gene expression, through a chromatin remodeling mechanism. In contrast, NaB or TSA do not increase H3K9-acetylation of ATP2A2 proximal promoter. In addition, treatment with 5-aza-2'-deoxycytidine did not affect SERCA2b and SERCA3a expression, suggesting that promoter methylation status does not alter their expression in these cell lines. We propose that alteration of SERCA2b/SERCA3a isoform expression ratio could affect calcium management within the cell, and thus, the cellular pathways regulated by calcium could be compromised, such as cellular proliferation or apoptosis. (C) 2015 Wiley Periodicals, Inc.

Esophageal adenocarcinoma (EAC) has become a major concern in Western countries due to rapid rises in incidence coupled with very poor survival rates. One of the key risk factors for the development of this cancer is the presence of Barrett's esophagus (BE), which is believed to form in response to repeated gastro-esophageal reflux. In this study we performed comparative, genome-wide expression profiling (using Illumina whole-genome Beadarrays) on total RNA extracted from esophageal biopsy tissues from individuals with EAC, BE (in the absence of EAC) and those with normal squamous epithelium. We combined these data with publically accessible raw data from three similar studies to investigate key gene and ontology differences between these three tissue states. The results support the deduction that BE is a tissue with enhanced glycoprotein synthesis machinery (DPP4, ATP2A3, AGR2) designed to provide strong mucosal defenses aimed at resisting gastro-esophageal reflux. EAC exhibits the enhanced extracellular matrix remodeling (collagens, IGFBP7, PLAU) effects expected in an aggressive form of cancer, as well as evidence of reduced expression of genes associated with mucosal (MUC6, CA2, TFF1) and xenobiotic (AKR1C2, AKR1B10) defenses. When our results are compared to previous whole-genome expression profiling studies keratin, mucin, annexin and trefoil factor gene groups are the most frequently represented differentially expressed gene families. Eleven genes identified here are also represented in at least 3 other profiling studies. We used these genes to discriminate between squamous epithelium, BE and EAC within the two largest cohorts using a support vector machine leave one out cross validation (LOOCV) analysis. While this method was satisfactory for discriminating squamous epithelium and BE, it demonstrates the need for more detailed investigations into profiling changes between BE and EAC.