From Nicotine to Breast Cancer, Implications of Cholinergic Receptor Pathway

Abstract

Nicotine is the most important pharmacologically active compound in all forms of tobacco smoke because of its interaction with cholinergic receptors. In the current issue of the Journal, a research article by Lee et al. (1) and a brief communication by Falvella et al. (2) use different approaches to contribute to a better understanding of the roles of nicotine receptors and the biological basis that underlies the environmental and genetic components of smoking-related cancer risk. Two types of acetylcholine receptors (AChRs) exist: the nicotinic AChRs (nAChRs) and muscarinic AChRs (mAChRs). The nAChRs are ligand-gated ion channels and form pentameric complexes that consist of four related but genetically and immunologically distinct subunits: a, b, g, and d (3). The a9-nAChR, a known homopentamer that plays a central role in coordinating keratinocyte adhesion and motility during wound healing (4), is encoded by a gene (CHRNA9) on human chromosome 4p (5). Lee et al. (1) showed that a9-nAChRs were ubiquitously expressed in many epithelial and cancer cell lines from lung and breast and that most of the same cell lines also expressed a5- and a10-nAChRs. The a9-nAChRs were also present in primary tumors and nonmalignant breast tissue obtained from patients; however, cancers had increased a9-nAChR expression compared with the surrounding