Enhanced Sensitivity to Cytochrome c–Induced Apoptosis Mediated by PHAPI in Breast Cancer Cells
| Autor: | Jeffrey R. Marks, Zachary T. Schafer, Kevin M. Wright, Amanda B. Parrish, Mohanish Deshmukh, Seth S. Margolis, Sally Kornbluth |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
medicine.medical_specialty Cytochrome Apoptosis Breast Neoplasms Biology medicine.disease_cause Cytosol Cell Line Tumor Internal medicine medicine Humans APAF1 Caspase-9 Cytochrome c Intracellular Signaling Peptides and Proteins Cytochromes c Nuclear Proteins Proteins RNA-Binding Proteins Caspase 9 Mitochondria Protein Structure Tertiary Enzyme Activation Apoptotic Protease-Activating Factor 1 Endocrinology Oncology Caspases Cancer cell biology.protein Cancer research Apoptosome Carcinogenesis |
| Zdroj: | Cancer Research. 66:2210-2218 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-05-3923 |
| Popis: | Apoptotic signaling defects both promote tumorigenesis and confound chemotherapy. Typically, chemotherapeutics stimulate cytochrome c release to the cytoplasm, thereby activating the apoptosome. Although cancer cells can be refractory to cytochrome c release, many malignant cells also exhibit defects in cytochrome c–induced apoptosome activation, further promoting chemotherapeutic resistance. We have found that breast cancer cells display an unusual sensitivity to cytochrome c–induced apoptosis when compared with their normal counterparts. This sensitivity, not observed in other cancers, resulted from enhanced recruitment of caspase-9 to the Apaf-1 caspase recruitment domain. Augmented caspase activation was mediated by PHAPI, which is overexpressed in breast cancers. Furthermore, cytochrome c microinjection into mammary epithelial cells preferentially killed malignant cells, suggesting that this phenomenon might be exploited for chemotherapeutic purposes. (Cancer Res 2006; 66(4): 2210-8) |
| Databáze: | OpenAIRE |
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