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Nicotine promotes mammary tumor migration via a signaling cascade involving protein kinase C and CDC42

Guo, Jinjin
Ibaragi, Soichiro
Zhu, Tongbo
Luo, Ling-Yu
Hu, Guo-Fu
Chen, Chang Yan
Published in Cancer research. 2008, vol. 68, no. 20, p. 8473-81
Abstract Nicotine, one of the major components in tobacco, is at high concentrations in the bloodstream of cigarette smokers. However, the mechanisms of how nicotine affects tumor development and whether nicotine is a potential carcinogen for malignancies induced by secondhand smoking are not fully understood yet. Here, we investigate the signaling pathways by which nicotine potentiates tumorigenesis in human mammary epithelial-like MCF10A or cancerous MCF7 cells. We show that human MCF10A and MCF7 cells both express four subunits of nicotine acetylcholine receptor (nAChR). The treatment of these cells with nicotine enhances the activity of protein kinase C (PKC) alpha without altering the expression level of this kinase. Nicotine also stimulates [(3)H]thymidine incorporation into the genome of these cells as well as forces serum-starved cells to enter S phase of the cell cycle, resulting in growth promotion. Importantly, on nicotine treatment, the mobility of MCF10A and MCF7 cells is enhanced, which can be blocked by the addition of nAChR or PKC inhibitor. Experiments using small interfering RNA knockdown or ectopic expression of cdc42 showed that cdc42 functions as a downstream effector of PKC and is crucial in the regulation of nicotine-mediated migratory activity in the cells. Together, our findings suggest that nicotine, through interacting with its receptor, initiates a signaling cascade that involves PKC and cdc42 and consequently promotes migration in mammary epithelial or tumor cells.
Keywords AnimalsBreast/drug effects/enzymologyBreast Neoplasms/pathologyCell Cycle/drug effectsCell Line, TumorCell Movement/drug effectsCell Proliferation/drug effectsHumansLung Neoplasms/secondaryMiceNicotine/toxicityProtein Kinase C-alpha/physiologySignal Transduction/drug effectsCdc42 GTP-Binding Protein/physiology
PMID: 18922921
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Research group L'imagerie cérébrale (184)
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GUO, Jinjin et al. Nicotine promotes mammary tumor migration via a signaling cascade involving protein kinase C and CDC42. In: Cancer research, 2008, vol. 68, n° 20, p. 8473-81. https://archive-ouverte.unige.ch/unige:2523

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Deposited on : 2009-08-27

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