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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Most colon cancers overexpress M3 muscarinic receptors (M3R), and post-M3R signaling stimulates human colon cancer cell proliferation. Acetylcholine (ACh), a muscarinic receptor ligand traditionally regarded as a neurotransmitter, may be produced by nonneuronal cells. We hypothesized that ACh release by human colon cancer cells results in autocrine stimulation of proliferation. H508 human colon cancer cells, which have robust M3R expression, were used to examine effects of muscarinic receptor antagonists, acetylcholinesterase inhibitors, and choline transport inhibitors on cell proliferation. A nonselective muscarinic receptor antagonist (atropine), a selective M3R antagonist (p-fluorohexahydro-sila-difenidol hydrochloride), and a choline transport inhibitor (hemicholinum-3) all inhibited unstimulated H508 colon cancer cell proliferation by approximately 40% (P<0.005). In contrast, two acetylcholinesterase inhibitors (eserine-hemisulfate and bis-9-amino-1,2,3,4-tetrahydroacridine) increased proliferation by 2.5- and 2-fold, respectively (P<0.005). By using quantitative real-time PCR, expression of choline acetyltransferase (ChAT), a critical enzyme for ACh synthesis, was identified in H508, WiDr, and Caco-2 colon cancer cells. By using high-performance liquid chromatography-electrochemical detection, released ACh was detected in H508 and Caco-2 cell culture media. Immunohistochemistry in surgical specimens revealed weak or no cytoplasmic staining for ChAT in normal colon enterocytes (n=25) whereas half of colon cancer specimens (n=24) exhibited moderate to strong staining (P<0.005). We conclude that ACh is an autocrine growth factor in colon cancer. Mechanisms that regulate colon epithelial cell production and release of ACh warrant further investigation.
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PMID:Acetylcholine release by human colon cancer cells mediates autocrine stimulation of cell proliferation. 1865 26

We used immunochemistry to demonstrate expression of acetylcholine's nicotinic alpha7-receptor subtype in human colon cancer cell line HT-29. Moreover, RT-PCR and immunochemistry showed that choline acetyltransferase and acetylcholine esterase, the enzymes responsible for acetylcholine synthesis and degradation, respectively, localise in HT-29 cells. Bromoacetylcholine bromide, an inhibitor of choline acetyltransferase, significantly attenuated basal cell growth. Our findings suggest that acetylcholine might serve as an autocrine/paracrine-or speculatively, even intracrine-signalling molecule in cell line HT-29, thus contributing to carcinogenesis/cancer progression.
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PMID:Is acetylcholine an autocrine/paracrine growth factor via the nicotinic alpha7-receptor subtype in the human colon cancer cell line HT-29? 1928 65

An elderly man with long-standing, nonresectable pheochromocytoma had rapid development of rectal adenocarcinoma despite close endoscopic surveillance. We determined that the patient's colorectal cancer overexpressed muscarinic receptor subtype 3, whereas his pheochromocytoma expressed choline acetyltransferase, an enzyme required to produce acetylcholine, which is a muscarinic receptor agonist. These findings suggested that acetylcholine release from the pheochromocytoma stimulated rapid growth of the rectal neoplasm. As proof of principle, we found that culture media conditioned by pheochromocytoma cells stimulates proliferation of a human colon cancer cell line, an effect attenuated by atropine, a muscarinic receptor inhibitor. Our observations provide both clinical and laboratory evidence that muscarinic receptor agonists promote the growth of colorectal neoplasia.
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PMID:Bedside to bench: role of muscarinic receptor activation in ultrarapid growth of colorectal cancer in a patient with pheochromocytoma. 2410 Jan 92