Abstract | BACKGROUND: METHODS: RESULTS: When euthanized at week 20, control mice had 8.0 ± 1.3 tumors per animal, whereas bethanechol-treated mice had 10.4 ± 1.5 tumors per mouse (mean ± SE; P = 0.023), a 30% increase. Strikingly, tumor volume per animal was increased 52% in bethanechol-treated compared with control mice (179.7 ± 21.0 vs. 111. 8 ± 22.4 mm(3); P = 0.047). On histological examination, bethenechol-treated mice also had more adenocarcinomas per animal (8.0 ± 1.0 vs. 4.1 ± 0.6 for control mice, P = 0.0042). Cell proliferation in both normal mucosa and adenocarcinomas was increased in bethanechol-treated compared to control mice. Also, in tumors, bethanechol treatment increased expression of Chrm3, Egfr and post-Egfr signaling molecules Myc and cyclin D1. Bethanechol treatment increased the thickness of normal colonic mucosa and the expression of selected matrix metalloproteinase ( Mmp) genes, including Mmp7, Mmp10 and Mmp13. CONCLUSIONS: These findings support a prominent role for muscarinic receptors in colon neoplasia, and identify post-receptor signaling molecules as potential therapeutic targets.
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Authors | Zhongsheng Peng, Jonathon Heath, Cinthia Drachenberg, Jean-Pierre Raufman, Guofeng Xie |
Journal | BMC cancer
(BMC Cancer)
Vol. 13
Pg. 204
(Apr 24 2013)
ISSN: 1471-2407 [Electronic] England |
PMID | 23617763
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- HIF1A protein, human
- Hypoxia-Inducible Factor 1, alpha Subunit
- Muscarinic Agonists
- Myc protein, mouse
- Proto-Oncogene Proteins c-myc
- RNA, Messenger
- Receptor, Muscarinic M3
- Bethanechol
- Cyclin D1
- Cyclooxygenase 2
- ErbB Receptors
- Matrix Metalloproteinase 13
- Matrix Metalloproteinase 10
- Matrix Metalloproteinase 7
- Azoxymethane
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Topics |
- Adenocarcinoma
(chemically induced, metabolism, pathology)
- Animals
- Azoxymethane
- Bethanechol
(pharmacology)
- Cell Proliferation
(drug effects)
- Cell Transformation, Neoplastic
(drug effects)
- Colonic Neoplasms
(chemically induced, metabolism, pathology)
- Cyclin D1
(genetics)
- Cyclooxygenase 2
(genetics)
- ErbB Receptors
(genetics)
- Gene Expression
(drug effects)
- Hypoxia-Inducible Factor 1, alpha Subunit
(genetics)
- Intestinal Mucosa
(drug effects, pathology)
- Male
- Matrix Metalloproteinase 10
(genetics)
- Matrix Metalloproteinase 13
(genetics)
- Matrix Metalloproteinase 7
(genetics)
- Mice
- Muscarinic Agonists
(pharmacology)
- Proto-Oncogene Proteins c-myc
(genetics)
- RNA, Messenger
(metabolism)
- Receptor, Muscarinic M3
(metabolism)
- Signal Transduction
(drug effects)
- Tumor Burden
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