May, 2010
Protein Expression Profiles of Necrosis and Apoptosis Induced by 5-Fluoro-2 '-deoxyuridine in Mouse Cancer Cells
JOURNAL OF PROTEOME RESEARCH
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- Volume
- 9
- Number
- 5
- First page
- 2329
- Last page
- 2338
- Language
- English
- Publishing type
- Research paper (scientific journal)
- DOI
- 10.1021/pr9010537
- Publisher
- AMER CHEMICAL SOC
We have investigated the molecular mechanisms regulating the necrosis and apoptosis that occur on treatment of mouse mammary tumor FM3A cells with 5-fluoro-2'-deoxyuridine (FUdR), a potent anticancer agent, using the original clone F28-7 and its variant F28-7-A cells. Previously, we reported an interesting observation that FUdR induces a necrotic morphology in F28-7 but an apoptotic morphology in F28-7-A cells. We have now analyzed the protein expression profiles of these FUdR-induced necrosis and apoptosis. Thus, proteome analysis of these clones by two-dimensional gel electrophoresis and mass spectrometry showed that the cytoplasmic intermediate filament protein, cytokeratin-19, is expressed at a significantly higher level in F28-7 than in F28-7-A cells. This strong expression was detected both in untreated and FUdR-treated stages of F28-7 cells. We interpreted this phenomenon as suggesting that cytokeratin-19 possesses a function in leading the cell to apoptosis. We performed a knockdown of cytokeratin-19 expression in F28-7 cells by use of the small interfering RNA technique. Indeed, a lowering of the cytokeratin-19 expression down to the level in F28-7-A occurred, and the FUdR-induced death morphology of this knockdown F28-7 was apoptosis, instead of the necrosis usually observable in the FUdR-treated F28-7. It is known that the cytoskeletal protein cytokeratin-19 undergoes caspase-mediated degradation during apoptosis. Our present finding provides an interesting possibility that cytokeratin-19 may have a key role in regulating cell-death morphology.
- Link information
- ID information
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- DOI : 10.1021/pr9010537
- ISSN : 1535-3893
- Pubmed ID : 20155980
- Web of Science ID : WOS:000277353200024