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Signaling Pathway Through Which Nicotine Promotes Breast Cancer Migration Discovered

GEN News Highlights – 13 Oct 08

Researchers at the Beth Israel Deaconess Medical Center determined that breast epithelial-like MCF10A cells and cancerous MCF7 cells both express four subunits of nicotine receptor nAChR. When bound, it initiates a signaling process that promotes migration in mammary epithelial or tumor cells.

The treatment of these cells with nicotine enhanced the activity of protein kinase C (PKC)   without changing its expression level, the scientists reports. Nicotine also stimulated [3H]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.

Also on nicotine treatment, the mobility of MCF10A and MCF7 cells was enhanced, which could be blocked by the addition of nAChR or PKC inhibitor, the research team adds. Experiments using siRNA 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.

“The best known role of nAChR is in the nerve system,” according to Chang Yan Chen, Ph.D., M.D., lead author of the study. “Although cells from various tissue origins express different subunits of nAChR, we know very little about the functions of nAChR in nonneuronal cells and tissues, in particular in mammary cells.”

When injected into the tail of a mouse, the cancerous MCF7 cells migrated to the lungs. In vivo and in vitro studies indicated that nicotine is not a conventional carcinogen, thus no metastasis occurs with nicotine alone, according to the researchers. Rather, they say that it combines with other factors to enable tumorigenesis.

Scientists say the next step is to explore the effects of nicotine in relation to first- and second-hand exposure on breast cancer initiation and development. In particular, they want to study genetic backgrounds with loss or defect of different tumor suppressors.

The paper appears in Cancer Research.

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