Sensitization to the lysosomal cell death pathway upon immortalization and transformation.

Journal article

Tumorigenesis is associated with several changes that alter the cellular susceptibility to programmed cell death. Here, we show that immortalization and transformation sensitize cells in particular to the cysteine cathepsin-mediated lysosomal death pathway. Spontaneous immortalization increased the susceptibility of wild-type murine embryonic fibroblasts (MEFs) to tumor necrosis factor (TNF)-mediated cytotoxicity >1000-fold, whereas immortalized MEFs deficient for lysosomal cysteine protea...

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Authors: Fehrenbacher, N; Gyrd-Hansen, M; Poulsen, B; Felbor, U; Kallunki, T

• Journal: Cancer research
• Volume: 64
• Issue: 15
• Pages: 5301-5310
• Publication date: 2004-08-01
• DOI: 10.1158/0008-5472.can-04-1427
• EISSN: 1538-7445
• ISSN: 0008-5472
• Language: English
• Keywords: Apoptosis; Tumor Necrosis Factor-alpha; Lysosomes; RNA Interference; Embryo, Mammalian; Transfection; Cysteine Endopeptidases; Caspases; Mice; Cathepsin D; Fibroblasts; Caspase Inhibitors; Cathepsin L; Mice, Knockout; Cell Transformation, Neoplastic; Cytochromes c; Animals; Genes, src; Mice, Inbred C57BL; Drug Resistance, Neoplasm; NIH 3T3 Cells; Signal Transduction; Cathepsin B; Antineoplastic Agents; Cathepsins; Enzyme Inhibitors; Enzyme Activation; Caspase 3; Genes, ras