Nicotine Promotes Growth Of Tumors Already Established By Tobacco Carcinogens

nAChRs function mainly in the neuronal system, however recent studies have shown their expression and function in non-neuronal systems as well. In the current study, the authors show that stimulation of human non–small cell lung cancers (NSCLCs) as well as cells lining the air passages of the lung (known as bronchial cells) with a physiological concentration of nicotine leads to robust cell proliferation that is dependent on nAChRs.

Furthermore, nicotine appears to activate the major components of the cell proliferation cycle in a manner very reminiscent of growth factors. Specifically, nicotine stimulation leads to the binding of Raf-1 to Rb, activation of cyclin-dependent kinases, phosphorylation of Rb, and recruitment of E2F1 to proliferative promoters.

Previous studies had shown that interfering with the interaction of Rb and Raf-1 prevented cell growth and tumor growth. In the current study the same appears to be true for nicotine stimulation of cells. A role for the Rb–Raf-1 interaction in the genesis of lung cancer is further supported by the observation that there was more Raf-1 associated with Rb in 8 out of 10 tumor samples examined, compared to the adjacent normal tissues. These observations suggest a role for Rb–Raf-1 interaction in the genesis of lung cancer.

These studies shed new light on the previously unknown mechanisms underlying nicotine-induced cell proliferation in lung cancer cells – namely that functional nAChRs on bronchial cells as well as lung carcinoma cells enable nicotine to promote the growth of established tumors.