Stress-Related Signaling Pathways in Lethal and Nonlethal Prostate CancerHarvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA.;Univ Florida, Coll Med, Dept Epidemiol, Gainesville, FL USA.;Univ Florida, Coll Publ Hlth & Hlth Profess, Gainesville, FL USA..
Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA..
Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA.;Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.;St Orsola Marcello Malpighi Hosp, Addarii Inst, Pathol Unit, Bologna, Italy..
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA.;Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Univ, Sch Med, Boston, MA USA.;Brigham & Womens Hosp, Dept Med, Div Aging, 75 Francis St, Boston, MA 02115 USA..
Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA..
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..
Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA.;Harvard Univ, Sch Med, Boston, MA USA.;Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA..
Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.;Harvard Univ, Sch Med, Boston, MA USA.;Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA..
Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA.;Harvard Univ, Sch Med, Boston, MA USA.;Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA..
Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA.;Univ Orebro, Clin Epidemiol & Biostat, Fac Med & Hlth, SE-70182 Orebro, Sweden..
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2016 (Engelska)Ingår i: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 22, nr 3, s. 765-772Artikel i tidskrift (Refereegranskat) Published
Resurstyp
Text
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.
Ort, förlag, år, upplaga, sidor
2016. Vol. 22, nr 3, s. 765-772
Nationell ämneskategori
Cancer och onkologi
Identifikatorer
URN: urn:nbn:se:uu:diva-277987DOI: 10.1158/1078-0432.CCR-15-0101ISI: 000369083300026PubMedID: 26490316OAI: oai:DiVA.org:uu-277987DiVA, id: diva2:906096
Forskningsfinansiär
NIH (National Institute of Health), T32GM074897NIH (National Institute of Health), T32 CA09001NIH (National Institute of Health), CA136578NIH (National Institute of Health), CA090381Svenska Sällskapet för Medicinsk Forskning (SSMF)Cancerfonden, CAN 2013/6502016-02-232016-02-232022-10-31Bibliografiskt granskad