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

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

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.

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Acknowledgments

This work was supported by the Fundação de Amparo à Pesquisa do estado de Minas Gerais, FAPEMIG #PPM-CDS-00246-09, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Capes and Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq. The authors would like to thank Francisco de Oliveira Vieira for artwork help and the Pro-Rectory of Research of the Universidade Federal de Minas Gerais for additional financial support.

Conflict of interest

The authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. Serviço de Biologia Celular, Diretoria de Pesquisa e Desenvolvimento da Fundação Ezequiel Dias, Belo Horizonte, MG, Brazil

    Letícia da Conceição Braga, Luciana Maria Silva & Josiane Barbosa Piedade

  2. Departamento de Ginecologia e Obstetrícia da Faculdade de Medicina da, Universidade Federal de Minas Gerais, Avenida Professor Alfredo Balena, 190, Santa Efigênia, Belo Horizonte, MG, Brazil

    Agnaldo Lopes da Silva Filho

  3. Departamento de Ginecologia e Obstetrícia da Faculdade de Medicina da, Universidade Estadual de São Paulo “Júlio de Mesquita Filho”, Botucatu, SP, Brazil

    Letícia da Conceição Braga, Paulo Traiman & Agnaldo Lopes da Silva Filho

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  1. Letícia da Conceição Braga
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Correspondence to Agnaldo Lopes da Silva Filho.

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da Conceição Braga, L., Silva, L.M., Piedade, J.B. et al. Epigenetic and expression analysis of TRAIL-R2 and BCL2: on the TRAIL to knowledge of apoptosis in ovarian tumors. Arch Gynecol Obstet 289, 1061–1069 (2014). https://doi.org/10.1007/s00404-013-3060-0

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