Anti-TNFRSF10D (aa 249-263) polyclonal antibody

Large-scale projects, such as The Cancer Genome Atlas (TCGA), Human Epigenome Project (HEP) and Human Epigenome Atlas (HEA), provide an insight into DNA methylation and histone modification markers. Changes in the epigenome significantly contribute to the initiation and progression of cancer. The goal of the present study was to characterize the prostate cancer malignant transformation model using the CpG island methylation pattern. The Human Prostate Cancer EpiTect Methyl II Signature PCR Array was used to evaluate the methylation status of 22 genes in prostate cancer cell lines: PC3, PC3M, PC3MPro4 and PC3MLN4, each representing different metastatic potential in vivo. Subsequently, it was ascertained whether DNA methylation plays a role in the expression of these genes in prostate cancer cells. Hypermethylation of APC, DKK3, GPX3, GSTP1, MGMT, PTGS2, RASSF1, TIMP2 and TNFRSF10D resulted in downregulation of their expression in prostate cancer cell lines as compared to WT fibroblasts. Mining of the TCGA data deposited in the MetHC database found increases in the methylation status of these 9 genes in prostate cancer patients, further supporting the role of methylation in altering the expression of these genes in prostate cancer. Future studies are warranted to investigate the role of these proteins in prostate cancer development.

Multiple chromosomal regions are affected by deletions in cervical cancer (CC) genomes, but their consequence and target gene involvement remains unknown. Our single nucleotide polymorphism (SNP) array identified 8p copy number losses localized to an 8.4 Mb minimal deleted region (MDR) in 36% of CC. The 8p MDR was associated with tumor size, treatment outcome, and with multiple HPV infections. Genetic, epigenetic, and expression analyses of candidate genes at MDR identified promoter hypermethylation and/or inactivation of decoy receptors TNFRSF10C and TNFRSF10D in the majority of CC patients. TNFRSF10C methylation was also detected in precancerous lesions suggesting that this change is an early event in cervical tumorigenesis. We further demonstrate here that CC cell lines exhibiting downregulated expression of TNFRSF10C and/or TNFRSF10D effectively respond to TRAIL-induced apoptosis and this affect was synergistic in combination with DNA damaging chemotherapeutic drugs. We show that the CC cell lines harboring epigenetic inactivation of TRAIL decoy receptors effectively activate downstream caspases suggesting a critical role of inactivation of these genes in efficient execution of extrinsic apoptotic pathway and therapy response. Therefore, these findings shed new light on the role of genetic/epigenetic defects in TRAIL decoy receptor genes in the pathogenesis of CC and provide an opportunity to explore strategies to test decoy receptor gene inactivation as a biomarker of response to Apo2L/TRAIL-combination therapy. (C) 2015 Wiley Periodicals, Inc.