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Androgen receptor overexpression in prostate cancer in type 2 diabetes.
Mol. Metab. 8, 158-166:doi:10.1016/j.molmet.2017.11.013 (2017)
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
ISSN (print) / ISBN
2212-8778
e-ISSN
2212-8778
Zeitschrift
Molecular Metabolism
Quellenangaben
Band: 8,
Seiten: 158-166,
Artikelnummer: doi:10.1016/j.molmet.2017.11.013
Verlag
Elsevier
Verlagsort
Amsterdam
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed