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Title:
Androgen Receptor and Androgen-Responsive Gene FKBP5 Are Independent Prognostic Indicators for Esophageal Adenocarcinoma | Digestive Diseases and Sciences
Description:
Esophageal adenocarcinoma is a male-dominant disease, but the role of androgens is unclear. To examine the expression and clinical correlates of the androgen receptor (AR) and the androgen-responsive gene FK506-binding protein 5 (FKBP5) in esophageal adenocarcinoma. Expression of AR and FKBP5 was determined by immunohistochemistry. The effect of the AR ligand 5α-dihydrotestosterone (DHT) on the expression of a panel of androgen-responsive genes was measured in AR-positive and AR-negative esophageal adenocarcinoma cell lines. Correlations in expression between androgen-responsive genes were analyzed in an independent cohort of esophageal adenocarcinoma tissues. There was AR staining in 75 of 77 cases (97 %), and FKBP5 staining in 49 (64 %), all of which had nuclear AR. Nuclear AR with FKBP5 expression was associated with decreased median survival (451 vs. 2800 days) and was an independent prognostic indicator (HR 2.894, 95 % CI 1.396–6.002, p = 0.0043) in multivariable Cox proportional hazards models. DHT induced a significant increase in expression of the androgen-responsive genes FKBP5, HMOX1, FBXO32, VEGFA, WNT5A, and KLK3 only in AR-positive cells in vitro. Significant correlations in expression were observed between these androgen-responsive genes in an independent cohort of esophageal adenocarcinoma tissues. Nuclear AR and expression of FKBP5 is associated with decreased survival in esophageal adenocarcinoma.
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Keywords {🔍}
pubmed, article, google, scholar, cas, cancer, adenocarcinoma, androgen, central, fkbp, prostate, esophageal, expression, receptor, cell, androgenresponsive, oesophageal, research, genes, adelaide, smith, access, australia, gene, cells, esophagus, university, woodville, privacy, cookies, content, analysis, independent, prognostic, eric, protein, receptors, res, growth, author, hospital, supplementary, material, data, information, publish, search, palethorpe, ruszkiewicz, leach,
Topics {✒️}
amino/carboxyl interaction-deficient variants fk506-binding protein 51 month download article/chapter castration-resistant prostate cancer androgen receptor-mediated regulation article digestive diseases central polypurine tract ar ligand 5α-dihydrotestosterone androgen-responsive gene fkbp5 full article pdf androgen-responsive genes fkbp5 androgen receptors sp1 binding site article smith privacy choices/manage cookies eric smith prostate cancer cells prostate cancer development primary cell cultures distal enhancer element poor prognosis translational health research neoplastic prostate epithelium androgen-responsive genes related subjects hum gene ther negatively regulating akt cell death dis independent prognostic indicators independent prognostic indicator mol cell endocrinol endocr relat cancer androgen-regulated genes esophageal adenocarcinoma cells dihydrotestosterone-inducible dickkopf 1 activate responsive sites esophageal adenocarcinoma tissues esophageal adenocarcinoma identified sex steroid hormones pka signaling pathways androgen receptor expression bmc cancer european economic area male-dominant disease male predominance due 17 year delayed development long-range activation distal intronic enhancers promoter dna methylation lentivirus vectors encoding
Questions {❓}
- Androgens in endometrial carcinoma: the killer or helper?
- Oesophageal adenocarcinoma: the new epidemic in men?
- Patients with prostate cancer are less likely to develop oesophageal adenocarcinoma: could androgens have a role in the aetiology of oesophageal adenocarcinoma?
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headline:Androgen Receptor and Androgen-Responsive Gene FKBP5 Are Independent Prognostic Indicators for Esophageal Adenocarcinoma
description:Esophageal adenocarcinoma is a male-dominant disease, but the role of androgens is unclear. To examine the expression and clinical correlates of the androgen receptor (AR) and the androgen-responsive gene FK506-binding protein 5 (FKBP5) in esophageal adenocarcinoma. Expression of AR and FKBP5 was determined by immunohistochemistry. The effect of the AR ligand 5α-dihydrotestosterone (DHT) on the expression of a panel of androgen-responsive genes was measured in AR-positive and AR-negative esophageal adenocarcinoma cell lines. Correlations in expression between androgen-responsive genes were analyzed in an independent cohort of esophageal adenocarcinoma tissues. There was AR staining in 75 of 77 cases (97 %), and FKBP5 staining in 49 (64 %), all of which had nuclear AR. Nuclear AR with FKBP5 expression was associated with decreased median survival (451 vs. 2800 days) and was an independent prognostic indicator (HR 2.894, 95 % CI 1.396–6.002, p = 0.0043) in multivariable Cox proportional hazards models. DHT induced a significant increase in expression of the androgen-responsive genes FKBP5, HMOX1, FBXO32, VEGFA, WNT5A, and KLK3 only in AR-positive cells in vitro. Significant correlations in expression were observed between these androgen-responsive genes in an independent cohort of esophageal adenocarcinoma tissues. Nuclear AR and expression of FKBP5 is associated with decreased survival in esophageal adenocarcinoma.
datePublished:2015-10-14T00:00:00Z
dateModified:2015-10-14T00:00:00Z
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Adenocarcinoma of the esophagus
Androgen receptors
FK506-binding protein 5
Steroids
Prognosis
Gastroenterology
Hepatology
Oncology
Transplant Surgery
Biochemistry
general
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headline:Androgen Receptor and Androgen-Responsive Gene FKBP5 Are Independent Prognostic Indicators for Esophageal Adenocarcinoma
description:Esophageal adenocarcinoma is a male-dominant disease, but the role of androgens is unclear. To examine the expression and clinical correlates of the androgen receptor (AR) and the androgen-responsive gene FK506-binding protein 5 (FKBP5) in esophageal adenocarcinoma. Expression of AR and FKBP5 was determined by immunohistochemistry. The effect of the AR ligand 5α-dihydrotestosterone (DHT) on the expression of a panel of androgen-responsive genes was measured in AR-positive and AR-negative esophageal adenocarcinoma cell lines. Correlations in expression between androgen-responsive genes were analyzed in an independent cohort of esophageal adenocarcinoma tissues. There was AR staining in 75 of 77 cases (97 %), and FKBP5 staining in 49 (64 %), all of which had nuclear AR. Nuclear AR with FKBP5 expression was associated with decreased median survival (451 vs. 2800 days) and was an independent prognostic indicator (HR 2.894, 95 % CI 1.396–6.002, p = 0.0043) in multivariable Cox proportional hazards models. DHT induced a significant increase in expression of the androgen-responsive genes FKBP5, HMOX1, FBXO32, VEGFA, WNT5A, and KLK3 only in AR-positive cells in vitro. Significant correlations in expression were observed between these androgen-responsive genes in an independent cohort of esophageal adenocarcinoma tissues. Nuclear AR and expression of FKBP5 is associated with decreased survival in esophageal adenocarcinoma.
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Adenocarcinoma of the esophagus
Androgen receptors
FK506-binding protein 5
Steroids
Prognosis
Gastroenterology
Hepatology
Oncology
Transplant Surgery
Biochemistry
general
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