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Stress-Related Signaling Pathways in Lethal and Nonlethal Prostate Cancer
Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
Ohio State Univ, Dept Stat, 1958 Neil Ave, Columbus, OH 43210 USA.;Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.;Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA.;Univ Iceland, Sch Hlth Sci, Ctr Publ Hlth Sci, Fac Med, Reykjavik, Iceland..
Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
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2016 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 22, no 3, 765-772 p.Article in journal (Refereed) Published
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Abstract [en]

Purpose: Recent data suggest that neuroendocrine signaling may influence progression in some cancers. We aimed to determine whether genes within the five major stress-related signaling pathways are differentially expressed in tumor tissue when comparing prostate cancer patients with lethal and non-lethal disease. Experimental Design: We measured mRNA expression of 51 selected genes involved in predetermined stress-related signaling pathways (adrenergic, glucocorticoid, dopaminergic, serotoninergic, and muscarinic systems) in tumor tissue and normal prostate tissue collected from prostate cancer patients in the Physicians' Health Study (n = 150; n = 82 with normal) and the Health Professionals Follow-Up Study (n = 254; n = 120 with normal). We assessed differences in pathway expression in relation to prostate cancer lethality as the primary outcome and to biomarkers as secondary outcomes. Results: Differential mRNA expression of genes within the adrenergic (P = 0.001), glucocorticoid (P < 0.0001), serotoninergic (P = 0.0019), and muscarinic (P = 0.0045) pathways in tumor tissue was associated with the risk of lethality. The adrenergic pathway was also statistically significant (P = 0.001) when comparing against differential expression of genes not involved in the pathways. In adjacent normal prostate tissue, none of the pathways was clearly differentially expressed between lethal and nonlethal prostate cancer. The glucocorticoid and adrenergic pathways were associated with cell proliferation, while the glucocorticoid pathway was additionally associated with angiogenesis and perineural invasion. Conclusions: Our study suggests that stress-related signaling pathways, particularly the adrenergic and glucocorticoid, may be dysregulated in the tumors of men whose prostate cancer proves to be lethal, and motivates further investigation of these pathways in functional studies.

Place, publisher, year, edition, pages
2016. Vol. 22, no 3, 765-772 p.
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Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-277987DOI: 10.1158/1078-0432.CCR-15-0101ISI: 000369083300026PubMedID: 26490316OAI: oai:DiVA.org:uu-277987DiVA: diva2:906096
Funder
NIH (National Institute of Health), T32GM074897NIH (National Institute of Health), T32 CA09001NIH (National Institute of Health), CA136578NIH (National Institute of Health), CA090381Swedish Society for Medical Research (SSMF)Swedish Cancer Society, CAN 2013/650
Available from: 2016-02-23 Created: 2016-02-23 Last updated: 2017-11-30Bibliographically approved

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