Epigenetic and expression analysis of TRAIL-R2 and BCL2: on the TRAIL to knowledge of apoptosis in ovarian tumors

• Published in: Archives of gynecology and obstetrics Vol. 289; no. 5; pp. 1061 - 1069
• Main Authors: da Conceição Braga, Letícia, Silva, Luciana Maria, Piedade, Josiane Barbosa, Traiman, Paulo, da Silva Filho, Agnaldo Lopes
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2014; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Apoptosis; Apoptosis Regulatory Proteins - genetics; Carcinoma, Ovarian Epithelial; Cell Line, Tumor; Cystadenoma, Serous - genetics; Deoxyribonucleic acid; DNA; DNA Methylation; Endocrinology; Epigenesis, Genetic; Female; Gene Expression; Gynecologic Oncology; Gynecology; Human Genetics; Humans; Medicine; Medicine & Public Health; Metastasis; Middle Aged; Neoplasm Staging; Neoplasms, Glandular and Epithelial - genetics; Obstetrics/Perinatology/Midwifery; Ovarian cancer; Ovarian Neoplasms - genetics; Polymerase Chain Reaction; Promoter Regions, Genetic; Prospective Studies; Receptors, TNF-Related Apoptosis-Inducing Ligand - genetics; Receptors, TNF-Related Apoptosis-Inducing Ligand - metabolism; Statistics, Nonparametric; Tumors; DNA methylation; Gene expression; -; Ovarian tumors
• ISSN: 0932-0067; 1432-0711
• DOI: 10.1007/s00404-013-3060-0

Objective This study assesses TRAIL - R2 ( TNF-related apoptosis-inducing ligand receptor 2) and BCL2 (B cell CLL/lymphoma 2) expression as well as CpG island methylation within the TRAIL - R2 promoter in ovarian serous tumors and primary and metastatic serous EOC (epithelial ovarian cancer). Methods RNA and DNA were obtained from women with normal ovarian tissues ( n  = 18), ovarian serous cystadenoma tumors ( n  = 11) and serous EOC ( n  = 16) using Trizol ® . Quantitative PCR was performed to quantify the relative levels of TRAIL - R2 and BCL2 . The methylation frequency of the TRAIL - R3 promoter was assessed using a methylation-specific PCR assay after DNA bisulfite conversion. Differences between the groups were evaluated using the χ 2 , Mann–Whitney U or Kruskal–Wallis tests, as indicated. Results We identified TRAIL - R2 and BCL2 mRNA expressed in all ovarian tumor groups, and there were significant differences between the groups. Both genes had low expression levels in ovarian serous cystadenoma and primary EOC tumors when compared with metastatic EOC. Methylation of the TRAIL - R2 promoter was frequently observed in all groups; however, there were no statistically significant associations. Conclusions Primary EOC is associated with lower TRAIL - R2 and BCL2 expression levels, while metastatic EOC is associated with higher expression of these genes. Promoter DNA methylation was not related to this finding, suggesting there are other mechanisms involved in transcriptional control.