FOXA1 promotes tumor progression in prostate cancer and represents a novel hallmark of castration-resistant prostate cancer
| Autor: | Peter J. Wild, Matteo Montani, Fabian Huber, Michael Müntener, Josefine Gerhardt, Thomas Hermanns, Marc Beer, Glen Kristiansen |
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| Přispěvatelé: | University of Zurich, Kristiansen, G |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Hepatocyte Nuclear Factor 3-alpha
Male PCA3 medicine.medical_specialty Estrogen receptor 610 Medicine & health Kaplan-Meier Estimate Biology Pathology and Forensic Medicine Prostate cancer Castration Resistance Prostate Internal medicine 10049 Institute of Pathology and Molecular Pathology Biomarkers Tumor Tumor Cells Cultured medicine Humans RNA Small Interfering Aged Cell Proliferation Prostatic Neoplasms Middle Aged Prognosis medicine.disease G1 Phase Cell Cycle Checkpoints 2734 Pathology and Forensic Medicine 10062 Urological Clinic Endocrinology medicine.anatomical_structure 10022 Division of Surgical Research Hormone receptor Tumor progression Gene Knockdown Techniques Disease Progression Cancer research FOXA1 Orchiectomy |
| Popis: | Forkhead box protein A1 (FOXA1) modulates the transactivation of steroid hormone receptors and thus may influence tumor growth and hormone responsiveness in prostate cancer. We therefore investigated the correlation of FOXA1 expression with clinical parameters, prostate-specific antigen (PSA) relapse-free survival, and hormone receptor expression in a large cohort of prostate cancer patients at different disease stages. FOXA1 expression did not differ significantly between benign glands from the peripheral zone and primary peripheral zone prostate carcinomas. However, FOXA1 was overexpressed in metastases and particularly in castration-resistant cases, but was expressed at lower levels in both normal and neoplastic transitional zone tissues. FOXA1 levels correlated with higher pT stages and Gleason scores, as well as with androgen (AR) and estrogen receptor expression. Moreover, FOXA1 overexpression was associated with faster biochemical disease progression, which was pronounced in patients with low AR levels. Finally, siRNA-based knockdown of FOXA1 induced decreased cell proliferation and migration. Moreover, in vitro tumorigenicity was inducible by ARs only in the presence of FOXA1, substantiating a functional cooperation between FOXA1 and AR. In conclusion, FOXA1 expression is associated with tumor progression, dedifferentiation of prostate cancer cells, and poorer prognosis, as well as with cellular proliferation and migration and with AR signaling. These findings suggest FOXA1 overexpression as a novel mechanism inducing castration resistance in prostate cancer. |
| Databáze: | OpenAIRE |
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