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Potential upstream regulators of cannabinoid receptor 1 signaling in prostate cancer: A Bayesian network analysis of data from a tissue microarray
Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
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2014 (English)In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 74, no 11, 1107-1117 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND The endocannabinoid system regulates cancer cell proliferation, and in prostate cancer a high cannabinoid CB1 receptor expression is associated with a poor prognosis. Down-stream mediators of CB1 receptor signaling in prostate cancer are known, but information on potential upstream regulators is lacking. RESULTS Data from a well-characterized tumor tissue microarray were used for a Bayesian network analysis using the max-min hill-climbing method. In non-malignant tissue samples, a directionality of pEGFR (the phosphorylated form of the epidermal growth factor receptor) CB1 receptors were found regardless as to whether the endocannabinoid metabolizing enzyme fatty acid amide hydrolase (FAAH) was included as a parameter. A similar result was found in the tumor tissue, but only when FAAH was included in the analysis. A second regulatory pathway, from the growth factor receptor ErbB2 FAAH was also identified in the tumor samples. Transfection of AT1 prostate cancer cells with CB1 receptors induced a sensitivity to the growth-inhibiting effects of the CB receptor agonist CP55,940. The sensitivity was not dependent upon the level of receptor expression. Thus a high CB1 receptor expression alone does not drive the cells towards a survival phenotype in the presence of a CB receptor agonist. CONCLUSIONS The data identify two potential regulators of the endocannabinoid system in prostate cancer and allow the construction of a model of a dysregulated endocannabinoid signaling network in this tumor. Further studies should be designed to test the veracity of the predictions of the network analysis in prostate cancer and other solid tumors.

Place, publisher, year, edition, pages
2014. Vol. 74, no 11, 1107-1117 p.
Keyword [en]
prostate cancer, epidermal growth factor, cannabinoid receptor, fatty acid amide hydrolase, directed acyclic graph
National Category
Cancer and Oncology
URN: urn:nbn:se:umu:diva-91251DOI: 10.1002/pros.22827ISI: 000338039700004OAI: diva2:735780
Available from: 2014-07-31 Created: 2014-07-28 Last updated: 2014-07-31Bibliographically approved

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Häggström, JennyCipriano, MariateresaPlym Forshell, LinusPersson, EmmaHammarsten, PeterFowler, Christopher J.
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