Smoking-induced Human Breast Cancer Formation through Induction of α9-nicotinic Acetylcholine Receptor

Tobacco is a substance that contains human carcinogens and may contribute to the risk for tumor formation in the lung and colon via nicotinic acetylcholine receptors (nAChRs). Nicotine receptors are a family of ligand-gated ion channels that mediate the effects of the neurotransmitter acetylcholine and are among the most well-understood receptors. The α4β2 nAChR is known to exist in the central nervous system (CNS) and functions as a transmitter, whereas the α7-nAChR is a well-established molecule that is involved in lung cancer tumorigenesis. Previously, however, there was no direct evidence to provide a link between tobacco carcinogens and cellular molecules involved in breast tumorigenesis. Recently, two large cohort epidemiological studies undertaken in the USA and Japan have indicated that breast cancer risk is associated with both active and passive smoking. Analysis of α9-nAChR expression in clinical tumor tissues indicated that theα9-nAChR is important for tumor carcinogenesis in vivo and nicotine-induced transformation of normal human breast epithelial cells in vitro. Long-term exposure to estrogen and nicotine significantly increases α9-nAChR expression and forms a positively regulated loop and that can be blocked by several chemicals and natural compounds. In this paper, the structure and functional relationship of the nAChR will be discussed. The role of nAChR in breast cancer formation and its implication for prevention of cancer formation will also be discussed.