Reciprocal and Autonomous Glucocorticoid and Androgen Receptor Activation in Salivary Duct Carcinoma.
Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Hormonal
/ pharmacology
Benzamides
Biomarkers, Tumor
/ metabolism
Carcinoma, Ductal
/ drug therapy
Cell Line, Tumor
Cell Proliferation
Female
Hormone Antagonists
/ pharmacology
Humans
Male
Middle Aged
Mifepristone
/ pharmacology
Nitriles
Phenylthiohydantoin
/ analogs & derivatives
Receptors, Androgen
/ metabolism
Receptors, Glucocorticoid
/ antagonists & inhibitors
Salivary Gland Neoplasms
/ drug therapy
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 03 2020
01 03 2020
Historique:
received:
15
05
2019
revised:
01
10
2019
accepted:
22
11
2019
pubmed:
28
11
2019
medline:
5
1
2021
entrez:
28
11
2019
Statut:
ppublish
Résumé
To determine the expression of glucocorticoid receptor (GR) and androgen receptor (AR) in salivary duct carcinoma (SDC) and to analyze the role of these proteins in the development and management of this disease entity. We performed a phenotypic assessment of GR and AR localization and expression, and determined their association with clinicopathologic factors in 67 primary SDCs. Of the 67 primary tumors, 12 (18%) overexpressed GR protein, 30 (45%) had constitutive expression, and 25 (37%) had complete loss of expression. Reciprocal GR and AR expression was found in 32 (48%) tumors, concurrent constitutive GR and AR expression in 23 (34%), and simultaneous loss of both receptors and high GR with AR expressions were found in 12 (18%). GR overexpression was significantly associated with worse clinical outcomes. Our study, for the first time, demonstrates differential GR and AR expressions, autonomous GR and AR activation, and ligand-independent AR expression and activation in SDC cells. The findings provide critical information on the roles of GR and AR steroid receptors in SDC tumorigenesis and development of biomarkers to guide targeted steroid receptor therapy trials in patients with these tumors.
Identifiants
pubmed: 31772120
pii: 1078-0432.CCR-19-1603
doi: 10.1158/1078-0432.CCR-19-1603
pmc: PMC7056500
mid: NIHMS1544917
doi:
Substances chimiques
AR protein, human
0
Antineoplastic Agents, Hormonal
0
Benzamides
0
Biomarkers, Tumor
0
Hormone Antagonists
0
Nitriles
0
Receptors, Androgen
0
Receptors, Glucocorticoid
0
Phenylthiohydantoin
2010-15-3
Mifepristone
320T6RNW1F
enzalutamide
93T0T9GKNU
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1175-1184Subventions
Organisme : NIDCR NIH HHS
ID : HHSN268200900039C
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NIDCR NIH HHS
ID : U01 DE019765
Pays : United States
Informations de copyright
©2019 American Association for Cancer Research.
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