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Lutz, S.Z. ; Hennenlotter, J.* ; Scharpf, M.O.* ; Sailer, C. ; Fritsche, L. ; Schmid, V.* ; Kantartzis, K. ; Wagner, R. ; Lehmann, R. ; Berti, L. ; Peter, A. ; Staiger, H. ; Fritsche, A. ; Fend, A.* ; Todenhöfer, T.* ; Stenzl, A.* ; Häring, H.-U. ; Heni, M.

Androgen receptor overexpression in prostate cancer in type 2 diabetes.

Mol. Metab. 8, 158-166:doi:10.1016/j.molmet.2017.11.013 (2017)
Verlagsversion Postprint DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Objective: While prostate cancer does not occur more often in men with diabetes, survival is markedly reduced in this patient group. Androgen signaling is a known and major driver for prostate cancer progression. Therefore, we analyzed major components of the androgen signaling chain and cell proliferation in relation to type 2 diabetes. Methods: Tumor content of 70 prostate tissue samples of men with type 2 diabetes and 59 samples of patients without diabetes was quantified by an experienced pathologist, and a subset of 51 samples was immunohistochemically stained for androgen receptor (AR). mRNA expression of AR, insulin receptor isoform A (IR-A) and B (IR-B) IGF-1 receptor (IGF1R), Cyp27A1 and Cyp7B1, PSA gene KLK3, PSMA gene FOLH1, Ki-67 gene MKI67, and estrogen receptor beta (ESR2) were analyzed by RT-qPCR. Results: AR mRNA and protein expression were associated with the tumor content only in men with diabetes. AR expression also correlated with downstream targets PSA (KLK3) and PSMA (FOLH1) and increased cell proliferation. Only in diabetes, AR expression was correlated to higher IR-AIIR-B ratio and lower IR-B/IGF1R ratio, thus, in favor of the mitogenic isoforms. Reduced Cyp27A1 and increased Cyp7B1 expressions in tumor suggest lower levels of protective estrogen receptor ligands in diabetes. Conclusions: We report elevated androgen receptor signaling and activity presumably due to altered insulin/IGF-1 receptors and decreased levels of protective estrogen receptor ligands in prostate cancer in men with diabetes. Our results reveal new insights why these patients have a worse prognosis. These findings provide the basis for future clinical trials to investigate treatment response in patients with prostate cancer and diabetes. 2017 The Authors. Published by Elsevier GmbH.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Prostate Cancer ; Androgen Receptor: Insulin Receptor ; Igf-1 Receptor ; Cyp27a1 ; Cyp7b1; Insulin; Growth; Cells; Expression; Metformin; Estrogen; Binding
Sprache englisch
Veröffentlichungsjahr 2017
HGF-Berichtsjahr 2017
ISSN (print) / ISBN 2212-8778
e-ISSN 2212-8778
Zeitschrift Molecular Metabolism
Quellenangaben Band: 8, Heft: , Seiten: 158-166, Artikelnummer: doi:10.1016/j.molmet.2017.11.013 Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)
Institute of Experimental Genetics (IEG)
POF Topic(s) 90000 - German Center for Diabetes Research
Forschungsfeld(er) Helmholtz Diabetes Center
Genetics and Epidemiology
PSP-Element(e) G-502400-001
G-501900-065
G-502400-002
DOI 10.1016/j.molmet.2017.11.013
WOS ID WOS:000429084900014
Scopus ID 85039038532
PubMed ID 29249638
Erfassungsdatum 2017-12-12
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