Cell survival, DNA damage, and oncogenic transformation after a transient and reversible apoptotic response
| Autor: | Hoi Yan Wu, Ho Man Tang, Shan Shan Wang, Chung Sing Timothy Wong, Ming Chiu Fung, Ho Lam Tang, Kan Liu, Denise J. Montell, Wan Keung Lau, Kit Man Wong, Keng Hou Mak, Hiu Tung Law, C. Conover Talbot, Shaomin Hu |
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| Rok vydání: | 2012 |
| Předmět: |
Programmed cell death
Cell Survival Liver cytology DNA damage Antineoplastic Agents Apoptosis medicine.disease_cause Rats Sprague-Dawley HeLa Transcriptome Mice 03 medical and health sciences 0302 clinical medicine Depsipeptides medicine Animals Humans Myocytes Cardiac Molecular Biology Cells Cultured Oligonucleotide Array Sequence Analysis 030304 developmental biology Mice Inbred BALB C 0303 health sciences Ethanol biology Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Articles Cell Biology biology.organism_classification Rats 3. Good health Cell biology Gene expression profiling Cell Transformation Neoplastic Animals Newborn Liver Microscopy Fluorescence Cell Biology of Disease 030220 oncology & carcinogenesis Anti-Infective Agents Local NIH 3T3 Cells Carcinogenesis human activities DNA Damage HeLa Cells |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.e11-11-0926 |
| Popis: | Dying primary liver, NIH 3T3, and HeLa cells can reverse the advanced stage of apoptosis and survive even after incurring DNA damage. Some surviving cells harbor genetic alterations that result in phenotypic diversity, including oncogenic transformation. Apoptosis serves as a protective mechanism by eliminating damaged cells through programmed cell death. After apoptotic cells pass critical checkpoints, including mitochondrial fragmentation, executioner caspase activation, and DNA damage, it is assumed that cell death inevitably follows. However, this assumption has not been tested directly. Here we report an unexpected reversal of late-stage apoptosis in primary liver and heart cells, macrophages, NIH 3T3 fibroblasts, cervical cancer HeLa cells, and brain cells. After exposure to an inducer of apoptosis, cells exhibited multiple morphological and biochemical hallmarks of late-stage apoptosis, including mitochondrial fragmentation, caspase-3 activation, and DNA damage. Surprisingly, the vast majority of dying cells arrested the apoptotic process and recovered when the inducer was washed away. Of importance, some cells acquired permanent genetic changes and underwent oncogenic transformation at a higher frequency than controls. Global gene expression analysis identified a molecular signature of the reversal process. We propose that reversal of apoptosis is an unanticipated mechanism to rescue cells from crisis and propose to name this mechanism “anastasis” (Greek for “rising to life”). Whereas carcinogenesis represents a harmful side effect, potential benefits of anastasis could include preservation of cells that are difficult to replace and stress-induced genetic diversity. |
| Databáze: | OpenAIRE |
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