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Nicotine induces cell proliferation, invasion and epithelial-mesenchymal transition in a variety of human cancer cell lines.International Journal of Cancer, October 9, 2008 [Epub ahead of print]
Dasgupta P, Rizwani W, Pillai S, Kinkade R, Kovacs M, Rastogi S, Banerjee S, Carless M, Kim E, Coppola D, Haura E, Chellappan S.
Drug Discovery Program, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL.
Cigarette smoking is strongly correlated with the onset of nonsmall cell lung cancer (NSCLC). Nicotine, an active component of cigarettes, has been found to induce proliferation of lung cancer cell lines. In addition, nicotine can induce angiogenesis and confer resistance to apoptosis. All these events are mediated through the nicotinic acetylcholine receptors (nAChRs) on lung cancer cells. In this study, we demonstrate that nicotine can promote anchorage-independent growth in NSCLCs. In addition, nicotine also induces morphological changes characteristic of a migratory, invasive phenotype in NSCLCs on collagen gel. These morphological changes were similar to those induced by the promigratory growth factor VEGF. The proinvasive effects of nicotine were mediated by alpha7-nAChRs on NSCLCs. RT-PCR analysis showed that the alpha7-nAChRs were also expressed on human breast cancer and pancreatic cancer cell lines. Nicotine was found to promote proliferation and invasion in human breast cancer. The proinvasive effects of nicotine were mediated via a nAChR, Src and calcium-dependent signaling pathway in breast cancer cells. In a similar fashion, nicotine could also induce proliferation and invasion of Aspc1 pancreatic cancer cells. Most importantly, nicotine could induce changes in gene expression consistent with epithelial to mesenchymal transition (EMT), characterized by reduction of epithelial markers like E-cadherin expression, ZO-1 staining and concomitant increase in levels of mesenchymal proteins like vimentin and fibronectin in human breast and lung cancer cells. Therefore, it is probable that the ability of nicotine to induce invasion and EMT may contribute to the progression of breast and lung cancers. (c) 2008 Wiley-Liss, Inc.
PMID: 18844224 [PubMed - as supplied by publisher]
Link to Abstract: http://www.ncbi.nlm.nih.gov/pubmed/18844224
Nicotine Promotes Mammary Tumor Migration via a Signaling Cascade Involving Protein Kinase C and cdc42Nicotine, 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 [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. 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.
Cancer Research 68, 8473-8481, October 15, 2008. doi: 10.1158/0008-5472.CAN-08-0131
Jinjin Guo1, Soichiro Ibaragi2, Tongbo Zhu1, Ling-Yu Luo1, Guo-Fu Hu2, Petra S. Huppi3 and Chang Yan Chen1
1 Department of Radiation Oncology, Beth Israel Deaconess Medical Center and 2 Department of Pathology, Harvard Medical School, Boston, Massachusetts and 3 Department of Pediatrics, University of Geneva, Geneva, Switzerland
Requests for reprints: Chang Yan Chen, Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, 21-27 Burlington Avenue, Room 553C, Boston, MA 02215. Phone: 617-632-8513; Fax: 617-632-0635; E-mail: [url=mailto:firstname.lastname@example.org]email@example.com[/url] .
http://cancerres.aacrjournals.org/cgi/c ... 68/20/8473
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He launched a campaign at the start of National No Smoking Week on Jan. 15 to get the Royal Canadian Mint to produce a “Quit Quarter” that is specifically designed to help quit smoking. He hopes a Quit Quarter would especially encourage teenagers getting allowance from their parents to reconsider where they spend their money.“Kids don’t see the warning labels, because they never see the packets, they just get single cigarettes off their friends.” - Dr. John Oyston