Rabbit Anti-Human ABCA5 (a.a. 1401-1500) Polyclonal antibody

Background ATP-binding cassette (ABC) transporters play various roles in cancer biology and drug resistance, but their association with outcomes in serous epithelial ovarian cancer (EOC) is unknown. Methods The relationship between clinical outcomes and ABC transporter gene expression in two independent cohorts of high-grade serous EOC tumors was assessed with real-time quantitative polymerase chain reaction, analysis of expression microarray data, and immunohistochemistry. Associations between clinical outcomes and ABCA transporter gene single nucleotide polymorphisms were tested in a genome-wide association study. Impact of short interfering RNA-mediated gene suppression was determined by colony forming and migration assays. Association with survival was assessed with Kaplan-Meier analysis and log-rank tests. All statistical tests were two-sided. Results Associations with outcome were observed with ABC transporters of the "A" subfamily, but not with multidrug transporters. High-level expression of ABCA1, ABCA6, ABCA8, and ABCA9 in primary tumors was statistically significantly associated with reduced survival in serous ovarian cancer patients. Low levels of ABCA5 and the C-allele of rs536009 were associated with shorter overall survival (hazard ratio for death = 1.50; 95% confidence interval [CI] = 1.26 to 1.79; P = 6.5e-6). The combined expression pattern of ABCA1, ABCA5, and either ABCA8 or ABCA9 was associated with particularly poor outcome (mean overall survival in group with adverse ABCA1, ABCA5 and ABCA9 gene expression = 33.2 months, 95% CI = 26.4 to 40.1; vs 55.3 months in the group with favorable ABCA gene expression, 95% CI = 49.8 to 60.8; P = .001), independently of tumor stage or surgical debulking status. Suppression of cholesterol transporter ABCA1 inhibited ovarian cancer cell growth and migration in vitro, and statin treatment reduced ovarian cancer cell migration. Conclusions Expression of ABCA transporters was associated with poor outcome in serous ovarian cancer, implicating lipid trafficking as a potentially important process in EOC.

The pathological hallmark of Parkinson's disease (PD) is the presence of aggregated alpha-synuclein associated with lipids. Substantial evidence now exists to indicate that alpha-synuclein binds and interacts with regions of membranes that are enriched in lipids (lipid rafts). Lipids are transported around the brain by a group of proteins called ATP-Binding Cassette subfamily A (ABCA) transporters and in recent years there has been mounting evidence indicating that ABCA transporters regulate a number of neurodegenerative disease processes. Only recently a genome-wide association study reported that ABCA5 was genetically associated with a reduced risk for PD. However, very little is known about the role of lipids and ABCA5 in the pathological process of PD. In this study we investigate the impact of the lipid-raft lipid sphingomyelin on alpha-synuclein and ABCA5 expression. We also investigate in which primary human brain cells ABCA5 is expressed and whether the expression of ABCA5 is altered in PD brain. When SK-N-SH neuronal cells were treated with sphingomyelin the expression of both alpha-synuclein and ABCA5 was significantly increased, indicating sphingomyelin as a potential substrate for the ABCA5 transporter. ABCA5 was strongly expressed in neurons and moderately in microglia, with only weak expression observed in astrocytes and oligodendrocytes. The expression of ABCA5 was significantly elevated in PD brains compared to age- and gender-matched control brains, possibly as a protective response to the disease. These data provide new evidence indicating that lipid is important for alpha-synuclein pathology in PD.