Abstract 1523: The mechanism of action of BCL6 in glioblastoma
| Autor: | Melanie J. McConnell, Nicole M. Jones, Katerina Hatzi, Marie-Sophie Fabre, Dinindu S. Senanayake, Ari Melnick |
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| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | Cancer Research. 77:1523-1523 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2017-1523 |
| Popis: | Glioblastoma (GBM) is the most common and most deadly brain tumor to occur in adults. Initially patients respond to radiation and chemotherapy, which primarily work by causing large amounts of DNA damage, causing apoptosis of the cells. However, this process does not happen effectively in GBM and understanding how these cells resist cell death in response to therapy is key to improving the efficacy of treatment. BCL6 is a transcription factor that stops cell death in response to DNA damage. Recent work in our lab has shown BCL6 to be present in untreated GBM tumors and up-regulated in treated GBM cells. This evidence indicates that BCL6 may be used as a mechanism of therapy resistance by GBM cells. In this study, the objective was to determine the mechanism of action of BCL6 in GBM cells using luciferase reporter assays, quantitative chromatin immunoprecipitation (qChIP) and RNA sequencing. We observed that BCL6 was transcriptionally active in GBM as shown by a reduction in luciferase activity when BCL6 was present. qChIP experiments revealed that BCL6 binding changed over time and was different with different types of DNA-damaging treatment. Preliminary analysis of our RNA sequencing data has identified a unique subset of genes which are upregulated when BCL6 is inhibited and downregulated in response to chemotherapy. These changes indicate that these genes may be regulated by BCL6 in chemotherapy treated cells. All of these results illustrate that BCL6 appears to have an active and relevant function in GBM cells, which demonstrates that BCL6 is an attractive therapeutic target in GBM. Citation Format: Nicole M. Jones, Marie-Sophie Fabre, Dinindu Sachindra Senanayake, Katerina Hatzi, Ari M. Melnick, Melanie J. McConnell. The mechanism of action of BCL6 in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1523. doi:10.1158/1538-7445.AM2017-1523 |
| Databáze: | OpenAIRE |
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