Androgen receptor overexpression in prostate cancer in type 2 diabetes
| Autor: | 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. |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Adult
Glutamate Carboxypeptidase II Male IGF-1 receptor PSMA prostate-specific membrane antigen lcsh:Internal medicine Cyp7B1 25-hydroxycholesterol 7α-hydroxylase DHT dihydrotestosterone ER estrogen receptor IR-A insulin receptor isoform A OGTT oral glucose tolerance test SERM selective estrogen receptor modulator Cytochrome P450 Family 7 ADT androgen-deprivation therapy Cyp27A1 SREBP2 sterol regulatory element-binding protein 2 Receptor IGF Type 1 IGF1R insulin like growth factor-1 receptor Estrogen Receptor beta Humans lcsh:RC31-1245 Cyp7B1 Aged Aged 80 and over PSA prostate-specific antigen Prostate cancer Prostate Prostatic Neoplasms Middle Aged Prostate-Specific Antigen Insulin Receptor Igf-1 Receptor Cyp27a1 Cyp7b1 [Prostate Cancer Androgen Receptor] Receptor Insulin Androgen receptor Ki-67 Antigen Diabetes Mellitus Type 2 Receptors Androgen 27HC 27-hydroxycholesterol IR insulin receptor Antigens Surface Steroid Hydroxylases Cyp27A1 sterol 27-hydroxylase Cholestanetriol 26-Monooxygenase Kallikreins Original Article AR androgen receptor IR-B insulin receptor isoform B Insulin receptor |
| Zdroj: | Molecular Metabolism, Vol 8, Iss, Pp 158-166 (2018) Molecular Metabolism Mol. Metab. 8, 158-166:doi:10.1016/j.molmet.2017.11.013 (2017) |
| ISSN: | 2212-8778 |
| DOI: | 10.1016/j.molmet.2017.11.013 |
| Popis: | 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-A/IR-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. Highlights • Androgen receptor expression is elevated in prostate cancer in men with diabetes. • This correlates with altered IR and IGF-1R and protective estrogen receptor ligands. • Our results reveal new insights why these patients have worse prognosis. |
| Databáze: | OpenAIRE |
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