The etiology of cervical cancer depends primarily on infection with human papillomaviruses, but tobacco smoking is the most important behavioral risk factor for this cancer. Therefore, we have previously confirmed involvement of nicotinic acetylcholine receptors (nAChRs) in cervical cancer biology. In order to comprehensively evaluate the role of cholinergic signaling in cervical cells, we have addressed additional participation of muscarinic acetylcholine receptors (mAChRs).

We have studied the expression of mAChRs and cholinergic system components by reverse transcription PCR and Western blots, the motility of cervical cancer cells in cell culture, and the signaling from mAChRs via the ERK1/2 signaling pathway.

The cervical cancer cells HeLa, SiHa and CaSki express four of the five mAChRs, M1, M3, M4, and M5, and the acetylcholine (ACh) synthesizing and degrading enzymes choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), and vesicular ACh transporter (VAChT). mAChR-dependent signaling induces cervical cell motility, which requires ERK1/2 activation, and could be abrogated by mAChR antagonists.

The epidemiological finding that tobacco smoke raises the prevalence of cervical cancer has led to analysis of the cholinergic signaling in cervical biology and carcinogenesis. Cervical cancer cells express several nAChRs and mAChRs, whose activation leads to changes of cellular properties such as increased motility and proliferation that favor a carcinogenic phenotype. The signaling involves intracellular phosphorylation cascades including ERK1/2.

Copyright © 2012. Published by Elsevier Inc.

PMID: 22406505 [PubMed - as supplied by publisher] Source: National Library of Medicine.