Reference - Detail
| RRC ID | 18701 |
|---|---|
| Author | Shin VY, Jin HC, Ng EK, Sung JJ, Chu KM, Cho CH. |
| Title | Activation of 5-lipoxygenase is required for nicotine mediated epithelial-mesenchymal transition and tumor cell growth. |
| Journal | Cancer Lett |
| Abstract |
Nicotine is shown to be one of the carcinogenic agents for gastric cancer. Perturbation of epithelial-mesenchymal transition (EMT) results in loss of intracellular adhesions leading to tumor progression. In this study, we examined the underlying mechanism of the long-term effects of nicotine on tumor progression in human gastric cancer cells. Nicotine activated 5-lipoxygenase (5-LOX) in three gastric cancer cell lines (MKN-45, MKN-28 and AGS). Cells treated with nicotine dose- and time-dependently induced cell proliferation, invasion and suppressed apoptosis. In addition, cell cycle progression analysis revealed that activation of 5-LOX modulated the G1/S phase transition regulatory proteins and caused cell proliferation. MK886 (5-LOX activating protein inhibitor) mediated the induction of apoptosis by elevation of caspase-3 and Bax/Bcl2 ratio. Abrogation of 5-LOX repressed featured molecular markers of EMT (inactivation of E-cadherin and activation of transcriptional repressor Snail). Blockade of 5-LOX signaling resulted in downregulation of cyclin D1, matrix metalloproteinase (MMP-7, -9), urokinase plasminogen activator (uPA) and its receptor (uPAR), and pro-apoptotic proteins. Furthermore, suppression of Snail and induction of E-cadherin is extracellular signal-regulated kinase (Erk)-dependent. Thus, we conclude that the promotion effect of nicotine on cancer cell progression and EMT is mediated by Erk/5-LOX signaling pathway. |
| Volume | 292(2) |
| Pages | 237-45 |
| Published | 2010-6-28 |
| DOI | 10.1016/j.canlet.2009.12.011 |
| PII | S0304-3835(09)00718-6 |
| PMID | 20061081 |
| MeSH | Apoptosis Arachidonate 5-Lipoxygenase / metabolism* Base Sequence Blotting, Western Cell Cycle Cell Line, Tumor DNA Primers Disease Progression Enzyme Activation Epithelial Cells / cytology* Humans Mesoderm / cytology* Nicotine / pharmacology* Reverse Transcriptase Polymerase Chain Reaction Stomach Neoplasms / enzymology Stomach Neoplasms / pathology* |
| IF | 7.36 |
| Times Cited | 40 |
| WOS Category | ONCOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| Total number of mentions | 0 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | MKN45(RCB1001) |