Medulloblastoma
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Reports summarize medulloblastoma study results from University of Texas
2009 JUL 13 - (NewsRx.com) -- "Apoptosis, a key cellular response to therapeutic agents is often inactivated in tumor cells. In this study, we evaluated the expression of the tumor necrosis family of death receptors, DR4 and DR5, in medulloblastoma tumor samples and cell lines to determine if epigenetic modulation of gene expression could sensitize tumor cell lines to TRAIL-mediated apoptosis," researchers in the United States report. "Human medulloblastoma samples and cell lines were analyzed for DR4 and DR5 expression by quantitative PCR and immunofluorescence assays. Cell lines with downregulated expression of one or both genes were treated with the histone deacetylase inhibitor, MS-275, and the expression of DR4 and DR5 measured by quantitative PCR, Western blotting, flow cytometry and chromatin immunoprecipitation assays. Induction of apoptosis in the presence of MS-275 was evaluated by TUNEL assay and its ability to augment TRAIL-mediated cytotoxicity was determined by MTT assays, Western blotting and flow cytometry. Compared to normal cerebellum, DR4, but not DR5 expression was consistently downregulated in medulloblastoma tumor samples and in Daoy and D283 cell lines. Interestingly, MS-275 decreased cell growth and induced apoptosis in Daoy and D283 cells. In Daoy cells, this coincided with increased histone H3 and H4 acetylation at the DR4 promoter and enhanced DR4 gene and protein expression as well as elevated Caspase-8 activity. The involvement of DR4 in the cellular response to MS-275 was further confirmed by the observation that knockdown of DR4 and FADD abrogated apoptosis. Further, addition of TRAIL to MS-275 treated cells resulted in an enhancement of apoptosis, suggesting that the upregulated death receptors were functional," wrote D.G. Aguilera and colleagues, University of Texas. The researchers concluded: "Our study provides an understanding of the role of DR4 in apoptosis of medulloblastoma cell lines and suggests a potential contribution of aberrant histone deacetylation to the resistance of medulloblastoma cells to therapeutic death.." Aguilera and colleagues published their study in the Journal of Neuro - Oncology (Reactivation of death receptor 4 (DR4) expression sensitizes medulloblastoma cell lines to TRAIL. Journal of Neuro - Oncology, 2009;93(3):303-318). For additional information, contact V. Gopalakrishnan, University of Texas MD Anderson Cancer Center, Dept. of Pediatrics, 1515 Holcombe Blvd., Unit 853, Houston, TX 77030, USA. Publisher contact information for the Journal of Neuro - Oncology is: Springer, 233 Spring St., New York, NY 10013, USA. Keywords: United States, Houston, Apoptosis, Cytometry, Deacetylase, Diagnosis, Diagnostics, Enzyme Research, Medulloblastoma, Necrosis, Neuro-Oncology, Oncology, Therapy, Treatment, University of Texas. This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2009, Biotech Business Week via NewsRx.com.
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