The alpha 9-nicotinic acetylcholine receptor serves as a molecular target for breast cancer therapy

Yuan Soon Ho, Chia Hwa Lee, Chih Hsiung Wu

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Tobacco is a substance that contains human carcinogens and may contribute to the risk of tumor formation in the lung and colon via nicotinic acetylcholine receptors (nAChRs). Cigarette smoke is a complex mixture of many compounds, including nicotine, which is the major active and addictive component of tobacco. Nicotine and its specific metabolized carcinogens directly bind to nAChRs on the cell membrane and trigger the nAChR signaling cascade. nAChRs, a family of ligand-gated ion channels that mediate the effects of the neurotransmitter acetylcholine, are among the best understood receptors. The α4β2-nAChR is known to exist in the central nervous system and functions as a transmitter, whereas the α7-nAChR is a well-established molecule that is involved in lung cancer tumorigenesis. Previously, however, there had been 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 United States 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 has indicated that the α9-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 review, we describe recent advances in the understanding of the assembly, activity and biological functions of nicotinic receptors, as well as developments in the therapeutic application of nicotinic receptor ligands.

Original languageEnglish
Pages (from-to)246-251
Number of pages6
JournalJournal of Experimental and Clinical Medicine(Taiwan)
Volume3
Issue number6
DOIs
Publication statusPublished - Dec 2011

Fingerprint

Nicotinic Receptors
Nicotine
Breast Neoplasms
Carcinogens
Tobacco
Carcinogenesis
Breast
Ligand-Gated Ion Channels
Therapeutics
Neoplasms
Tobacco Smoke Pollution
Complex Mixtures
Smoke
Tobacco Products
Acetylcholine
Neurotransmitter Agents
Epidemiologic Studies
Lung Neoplasms
Japan
Estrogens

Keywords

  • Breast cancer
  • Cigarette smoke
  • Nicotinic acetylcholine receptor

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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title = "The alpha 9-nicotinic acetylcholine receptor serves as a molecular target for breast cancer therapy",
abstract = "Tobacco is a substance that contains human carcinogens and may contribute to the risk of tumor formation in the lung and colon via nicotinic acetylcholine receptors (nAChRs). Cigarette smoke is a complex mixture of many compounds, including nicotine, which is the major active and addictive component of tobacco. Nicotine and its specific metabolized carcinogens directly bind to nAChRs on the cell membrane and trigger the nAChR signaling cascade. nAChRs, a family of ligand-gated ion channels that mediate the effects of the neurotransmitter acetylcholine, are among the best understood receptors. The α4β2-nAChR is known to exist in the central nervous system and functions as a transmitter, whereas the α7-nAChR is a well-established molecule that is involved in lung cancer tumorigenesis. Previously, however, there had been 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 United States 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 has indicated that the α9-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 review, we describe recent advances in the understanding of the assembly, activity and biological functions of nicotinic receptors, as well as developments in the therapeutic application of nicotinic receptor ligands.",
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author = "Ho, {Yuan Soon} and Lee, {Chia Hwa} and Wu, {Chih Hsiung}",
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