Cisplatin and TNF-α downregulate transcription of Bcl-xL in murine malignant mesothelioma cells

S.A. Fox, D. Kusmiaty, S. Loh, Arunasalam Dharmarajan, M.J. Garlepp

    Research output: Contribution to journalArticle

    10 Citations (Scopus)

    Abstract

    Malignant mesothelioma (MM) is an aggressive and highly chemo-resistant tumour. In this study, we examined cisplatin-induced apoptosis in mouse models of this disease and investigated the role of constitutive and inducible expression of apoptosis related genes in this process. All of the four mouse MM cell lines examined expressed Bax, Bcl-xL, c-Myc, and caspase-3 but not Bcl-2. Cisplatin-induced apoptosis characterised by DNA fragmentation and cell death while caspase-3/7 was activated in 3 of 4 cell lines. Quantitation of basal gene expression showed significant differences but there was no correlation between single genes and cisplatin sensitivity. In the AC29 and AB1 models, both cisplatin and TNF-alpha downregulated Bcl-xL gene expression, indicating that this gene was a common transcriptional target in these cells. The findings of the present study provide insights into apoptotic mechanisms in mesothelioma cells and show similar patterns of gene expression to that reported in the human disease. (c) 2005 Elsevier Inc. All rights reserved.
    Original languageEnglish
    Pages (from-to)983-991
    JournalBiochemical and Biophysical Research Communications
    Volume337
    Issue number3
    DOIs
    Publication statusPublished - 2005

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