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

Braga, Letícia da Conceição; Silva, Luciana Maria; Piedade, Josiane Barbosa; Traiman, Paulo; Filho, Agnaldo Lopes da Silva

doi:10.1007/s00404-013-3060-0

Cited by 7 publications

(2 citation statements)

References 42 publications

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“…Many of these disease states have mechanisms that are still unknown. Such an example is in ovarian serous carcinoma where high expression of TRAIL-receptor 2 (TRAIL-R2) has been associated with the disease state ( Braga et al., 2014 ). This study also showed that higher levels of Bcl2 were associated with TRAIL-R2 and the disease state.…”

Section: Bcl2 and Bcl6 Protein Deregulation And Diseasementioning

confidence: 99%

Apoptosis in inner ear sensory hair cells

Morrill

2017

Journal of Otology

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Apoptosis, or controlled cell death, is a normal part of cellular lifespan. Cell death of cochlear hair cells causes deafness; an apoptotic process that is not well understood. Worldwide, 1.3 billion humans suffer some form of hearing loss, while 360 million suffer debilitating hearing loss as a direct result of the absence of these cochlear hair cells (Worldwide Hearing, 2014). Much is known about apoptosis in other systems and in other cell types thanks to studies done since the mid-20th century. Here we review current literature on apoptosis in general, and causes of deafness and cochlear hair cells loss as a result of apoptosis. The family of B-cell lymphoma (Bcl) proteins are among the most studied and characterized. We will review current literature on the Bcl2 and Bcl6 protein interactions in relation to apoptosis and their possible roles in vulnerability and survival of cochlear hair cells.

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Section: Bcl2 and Bcl6 Protein Deregulation And Diseasementioning

confidence: 99%

Apoptosis in inner ear sensory hair cells

Morrill

2017

Journal of Otology

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“…Previous studies from our group described different apoptosis-related genes as EOC biomarkers associated with disease prognosis [11][12][13]. Considering that aberrant miRNAs expression plays a key pathogenic role in different stages of the carcinogenesis process and is involved in the deregulation of several biological processes, including apoptosis, miRNA profile analysis may reveal new biomarkers that can be used for EOC prognosis and chemorresistance [14].…”

Section: Introductionmentioning

confidence: 99%

Three-Dimensional Cellular Arrangement in Epithelial Ovarian Cancer Cell Lines TOV-21G and SKOV-3 is Associated with Apoptosis-Related miRNA Expression Modulation

Lima

Silva

Gonçales

et al. 2018

Cancer Microenvironment

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Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, and the lack of chemoresistance biomarkers contributes to the poor prognosis. Cancer stem cells (CSC) have been investigated in EOC to understand its relationship with chemoresistance and recurrence. In this context, in vitro cultivation-models are important tools for CSC studies. MicroRNAs (miRNAs) play key roles in cancer, CSC regulation and apoptosis. Thus, this study aims to evaluate the tumorsphere model as CSC-enrichment method in EOC studies and investigate apoptosis-related miRNAs in tumorspheres-derived EOC cell lines. TOV-21G and SKOV-3 were cultured in monolayer and tumorspheres. Genetic profiles of cell lines were obtained using COSMIC database. CD24/CD44/CD146/CD177 and ALDH1 markers were evaluated in cell lines and tumorspheres-derived by flow cytometry. Eleven miRNAs were selected by in silico analysis for qPCR analysis. According to COSMIC, TOV-21G and SKOV-3 have eight and nine cancer-related mutations, respectively. TOV-21G showed a CD44/CD24/CD117/CD146/ALDH1 profile in both culture models; thus, no significant difference between cultivation models was identified. SKOV-3 showed a CD44/CD24/ CD117/CD146/ALDH1 profile in both culture models, although the tumorsphere model showed a significant increase in CD24 subpopulation (ovarian CSC-like). Among eleven miRNAs, we observed differences in miRNA expression between culture models. MiR-26a was overexpressed in TOV-21G tumorspheres, albeit downregulated in SKOV-3 tumorspheres. MiR-125b-5p, miR-17-5p and miR-221 was downregulated in tumorsphere model in both cell lines. Given that tumorsphere-derived SKOV-3 had a higher ratio of CD24 cells, we suggest that miR-26a, miR-125b-5p, miR-17-5p and miR-221 downregulation could be related to poor EOC prognosis.

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Restoring TRAIL Mediated Signaling in Ovarian Cancer Cells

Farooqı

Yaylım

Ozkan

et al. 2014

Arch. Immunol. Ther. Exp.

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Ovarian cancer has emerged as a multifaceted and genomically complex disease. Genetic/epigenetic mutations, suppression of tumor suppressors, overexpression of oncogenes, rewiring of intracellular signaling cascades and loss of apoptosis are some of the deeply studied mechanisms. In vitro and in vivo studies have highlighted different molecular mechanisms that regulate tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediated apoptosis in ovarian cancer. In this review, we bring to limelight, expansion in understanding systematical characterization of ovarian cancer cells has led to the rapid development of new drugs and treatments to target negative regulators of TRAIL mediated signaling pathway. Wide ranging synthetic and natural agents have been shown to stimulate mRNA and protein expression of death receptors. This review is compartmentalized into programmed cell death protein 4, platelet-derived growth factor signaling and miRNA control of TRAIL mediated signaling to ovarian cancer. Mapatumumab and PRO95780 have been tested for efficacy against ovarian cancer. Use of high-throughput screening assays will aid in dissecting the heterogeneity of this disease and increasing a long-term survival which might be achieved by translating rapidly accumulating information obtained from molecular and cellular studies to clinic researches.

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

Abstract: 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.

Cited by 7 publications

References 42 publications

Apoptosis in inner ear sensory hair cells

Apoptosis in inner ear sensory hair cells

Three-Dimensional Cellular Arrangement in Epithelial Ovarian Cancer Cell Lines TOV-21G and SKOV-3 is Associated with Apoptosis-Related miRNA Expression Modulation

Restoring TRAIL Mediated Signaling in Ovarian Cancer Cells

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