Potential upstream regulators of cannabinoid receptor 1 signaling in prostate cancer: a Bayesian network analysis of data from a tissue microarray.
| Title: | Potential upstream regulators of cannabinoid receptor 1 signaling in prostate cancer: a Bayesian network analysis of data from a tissue microarray. |
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| Authors: | Häggström J; Department of Statistics, Umeå School of Business and Economics, Umeå University, Umeå, Sweden.; Cipriano M; Forshell LP; Persson E; Hammarsten P; Stella N; Fowler CJ |
| Source: | The Prostate [Prostate] 2014 Aug; Vol. 74 (11), pp. 1107-17. Date of Electronic Publication: 2014 Jun 09. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Wiley-Liss Country of Publication: United States NLM ID: 8101368 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-0045 (Electronic) Linking ISSN: 02704137 NLM ISO Abbreviation: Prostate Subsets: MEDLINE |
| Imprint Name(s): | Publication: : Hoboken, NJ : Wiley-Liss; Original Publication: New York : Alan R. Liss, c1980- |
| MeSH Terms: | Prostatic Neoplasms/*pathology ; Prostatic Neoplasms/*physiopathology ; Receptor, Cannabinoid, CB1/*physiology ; Signal Transduction/*physiology ; Tissue Array Analysis/*methods; Amidohydrolases/physiology ; ErbB Receptors/physiology ; Membrane Glycoproteins/physiology ; Prostatic Neoplasms/diagnosis ; Erb-b2 Receptor Tyrosine Kinases/physiology ; Bayes Theorem ; Cell Proliferation ; Humans ; Male ; Prognosis ; Retrospective Studies ; Fatty Acid Amide Hydrolases |
| Abstract: | 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.; (© 2014 The Authors. The Prostate published by Wiley Periodicals, Inc.) |
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| Grant Information: | DA014486 United States DA NIDA NIH HHS |
| Contributed Indexing: | Keywords: cannabinoid receptor; directed acyclic graph; epidermal growth factor; fatty acid amide hydrolase; prostate cancer |
| Substance Nomenclature: | EC 3.5.- (Amidohydrolases); EC 2.7.10.1 (ErbB Receptors); 0 (Membrane Glycoproteins); 0 (Receptor, Cannabinoid, CB1); EC 2.7.10.1 (Erb-b2 Receptor Tyrosine Kinases); EC 3.5.1.- (Fatty Acid Amide Hydrolases); 0 (LRIG1 protein, human); EC 2.7.10.1 (ERBB2 protein, human) |
| Entry Date(s): | Date Created: 20140611 Date Completed: 20140821 Latest Revision: 20260128 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC4145668 |
| DOI: | 10.1002/pros.22827 |
| PMID: | 24913716 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't