Dihydrotestosterone promotes kidney cancer cell proliferation by activating the STAT5 pathway via androgen and glucocorticoid receptors.
Androgen Receptor Antagonists
/ pharmacology
Carcinoma, Renal Cell
/ genetics
Cell Line, Tumor
Cell Proliferation
/ drug effects
Dihydrotestosterone
/ pharmacology
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Kidney Neoplasms
/ genetics
Receptors, Androgen
/ physiology
Receptors, Glucocorticoid
/ physiology
STAT5 Transcription Factor
/ genetics
Signal Transduction
/ drug effects
Tumor Suppressor Proteins
/ genetics
Androgen receptor
Glucocorticoid receptor
Kidney neoplasms
STAT5 transcription factor
Journal
Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060
Informations de publication
Date de publication:
Sep 2019
Sep 2019
Historique:
received:
19
01
2019
accepted:
05
08
2019
pubmed:
12
8
2019
medline:
29
8
2019
entrez:
12
8
2019
Statut:
ppublish
Résumé
Androgen receptors (ARs) are expressed on a variety of cell types, and AR signaling plays an important role in tumor development and progression in several cancers. This in vitro study evaluated the effect of dihydrotestosterone (DHT) on the proliferation of renal cell carcinoma (RCC) cells in relation to AR status. Steroid hormone receptor expression was evaluated using RT-PCR and Western blotting. The effect of DHT on cell proliferation and STAT5 phosphorylation was evaluated in RCC cell lines (Caki-2, A498, and SN12C) and primary RCC cells using cell viability assays and Western blotting. ARs and glucocorticoid receptors (GRs) were knocked down with small interfering RNAs before assessing changes in cell proliferation and STAT5 activation. DHT treatment promoted cell proliferation and increased STAT5 phosphorylation regardless of AR status. The AR antagonist bicalutamide reduced kidney cancer cell proliferation, regardless of AR status. AR and GR knockdown blocked STAT5 activation and reduced cell proliferation in all RCC cell lines. In patient-derived primary cells, DHT enhanced cell proliferation and this effect was diminished by treatment with the AR antagonists bicalutamide and enzalutamide and the GR antagonist mifepristone. DHT promotes cell proliferation through STAT5 activation in RCC cells, regardless of AR status. DHT appears to utilize the AR and GR pathways to activate STAT5, and the inhibition of AR and GR showed antitumor activity in RCC cells. These data suggest that targeting AR and GR may be a promising new approach to the treatment of RCC.
Identifiants
pubmed: 31401673
doi: 10.1007/s00432-019-02993-1
pii: 10.1007/s00432-019-02993-1
doi:
Substances chimiques
Androgen Receptor Antagonists
0
Receptors, Androgen
0
Receptors, Glucocorticoid
0
STAT5 Transcription Factor
0
STAT5A protein, human
0
Tumor Suppressor Proteins
0
Dihydrotestosterone
08J2K08A3Y
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2293-2301Subventions
Organisme : Asan Institute for Life Sciences, Asan Medical Center
ID : 2014-012
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