Abstract | PURPOSE: EXPERIMENTAL DESIGN: hPEBP4 expression in clinical breast specimens was examined by Tissue Microarrays. RNA interference was used to silence hPEBP4 expression in MCF-7 breast carcinoma cells and the effects on cell proliferation, cell cycle progression, apoptosis, as well as underlying mechanisms, were investigated. RESULTS: hPEBP4 was found to be expressed in up to 50% of breast cancers but in only <4% of normal breast tissues. Silencing of hPEBP4 potentiated tumor necrosis factor-alpha ( TNF-alpha)-induced apoptosis and cell cycle arrest in MCF-7 cells, which was due to the increased mitogen-activated protein kinase activation and the enhanced phosphatidylethanolamine externalization. Further investigation showed that silencing of hPEBP4 in MCF-7 cells promoted TNF-alpha-induced stability of p53, up-regulation of phospho-p53ser15, p21waf/cip, and Bax, and down-regulation of Bcl-2 and Bcl-xL, which were shown to depend on extracellular signal-regulated kinase 1/2 and c-jun NH2-terminal kinase activation by hPEBP4 silencing. Moreover, the increased proportion of cells in the G0-G1 phase of cell cycle was observed in hPEBP4-silenced MCF-7 cells on TNF-alpha treatment and the expression of cyclin A and cyclin E was down-regulated more significantly. CONCLUSIONS:
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Authors | Xiaojian Wang, Nan Li, Hongzhe Li, Bin Liu, Jianming Qiu, Taoyong Chen, Xuetao Cao |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 11
Issue 20
Pg. 7545-53
(Oct 15 2005)
ISSN: 1078-0432 [Print] United States |
PMID | 16243830
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cyclin A
- Cyclin E
- Phosphatidylethanolamine Binding Protein
- Tumor Necrosis Factor-alpha
- Tumor Suppressor Protein p53
- Proto-Oncogene Proteins c-raf
- Mitogen-Activated Protein Kinase 1
- Mitogen-Activated Protein Kinase 3
- Mitogen-Activated Protein Kinases
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Topics |
- Apoptosis
(drug effects)
- Blotting, Western
- Breast Neoplasms
(genetics, metabolism, pathology)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cyclin A
(metabolism)
- Cyclin E
(metabolism)
- Female
- Gene Expression Regulation, Neoplastic
- Humans
- MAP Kinase Signaling System
(drug effects)
- Mitogen-Activated Protein Kinase 1
(metabolism)
- Mitogen-Activated Protein Kinase 3
(metabolism)
- Mitogen-Activated Protein Kinases
(metabolism)
- Phosphatidylethanolamine Binding Protein
(genetics, metabolism)
- Protein Binding
- Proto-Oncogene Proteins c-raf
(metabolism)
- RNA Interference
- Reverse Transcriptase Polymerase Chain Reaction
- Tumor Necrosis Factor-alpha
(pharmacology)
- Tumor Suppressor Protein p53
(metabolism)
- Up-Regulation
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