Isoform-specific Activities of Androgen Receptor and its Splice Variants in Prostate Cancer Cells.
omics data
ARv567es
ARv7
androgen receptor
prostate cancer
splice variants
Journal
Endocrinology
ISSN: 1945-7170
Titre abrégé: Endocrinology
Pays: United States
ID NLM: 0375040
Informations de publication
Date de publication:
01 03 2021
01 03 2021
Historique:
received:
17
06
2020
pubmed:
11
12
2020
medline:
11
9
2021
entrez:
10
12
2020
Statut:
ppublish
Résumé
Androgen receptor (AR) signaling continues to drive castration-resistant prostate cancer (CRPC) in spite of androgen deprivation therapy (ADT). Constitutively active shorter variants of AR, lacking the ligand binding domain, are frequently expressed in CRPC and have emerged as a potential mechanism for prostate cancer to escape ADT. ARv7 and ARv567es are 2 of the most commonly detected variants of AR in clinical samples of advanced, metastatic prostate cancer. It is not clear if variants of AR merely act as weaker substitutes for AR or can mediate unique isoform-specific activities different from AR. In this study, we employed LNCaP prostate cancer cell lines with inducible expression of ARv7 or ARv567es to delineate similarities and differences in transcriptomics, metabolomics, and lipidomics resulting from the activation of AR, ARv7, or ARv567es. While the majority of target genes were similarly regulated by the action of all 3 isoforms, we found a clear difference in transcriptomic activities of AR versus the variants, and a few differences between ARv7 and ARv567es. Some of the target gene regulation by AR isoforms was similar in the VCaP background as well. Differences in downstream activities of AR isoforms were also evident from comparison of the metabolome and lipidome in an LNCaP model. Overall our study implies that shorter variants of AR are capable of mediating unique downstream activities different from AR and some of these are isoform specific.
Identifiants
pubmed: 33300995
pii: 6029774
doi: 10.1210/endocr/bqaa227
pmc: PMC8253248
pii:
doi:
Substances chimiques
AR protein, human
0
Mutant Proteins
0
Protein Isoforms
0
Receptors, Androgen
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA125123
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES030285
Pays : United States
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Références
Int J Mol Sci. 2017 Mar 27;18(4):
pubmed: 28346372
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
Oncotarget. 2016 Sep 27;7(39):64447-64470
pubmed: 27487144
Cancer Res. 2005 Oct 1;65(19):8887-95
pubmed: 16204060
Neoplasia. 2014 May;16(5):390-402
pubmed: 25016594
Neoplasia. 2013 Sep;15(9):1009-17
pubmed: 24027426
PLoS One. 2011 Apr 28;6(4):e19059
pubmed: 21552559
Nucleic Acids Res. 2018 Feb 28;46(4):1895-1911
pubmed: 29309643
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
N Engl J Med. 2014 Sep 11;371(11):1028-38
pubmed: 25184630
Oncotarget. 2015 Oct 13;6(31):31997-2012
pubmed: 26378018
Clin Cancer Res. 2020 Apr 15;26(8):1965-1976
pubmed: 31932493
Eur Urol Focus. 2018 Dec;4(6):907-915
pubmed: 28753886
Nat Protoc. 2016 Sep;11(9):1650-67
pubmed: 27560171
Endocrinology. 1996 Oct;137(10):4468-74
pubmed: 8828509
PLoS One. 2011;6(11):e27970
pubmed: 22114732
Mol Endocrinol. 1995 May;9(5):605-15
pubmed: 7565807
Can J Biochem Physiol. 1959 Aug;37(8):911-7
pubmed: 13671378
Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17492-7
pubmed: 24101480
Cancer Res. 2009 Jan 1;69(1):16-22
pubmed: 19117982
PLoS One. 2012;7(11):e48889
pubmed: 23152813
Int J Biochem Cell Biol. 2014 Sep;54:49-59
pubmed: 25008967
Cancer Res. 2011 Dec 15;71(24):7376-86
pubmed: 21990318
Metabolites. 2018 Jul 13;8(3):
pubmed: 30011843
Prostate Cancer Prostatic Dis. 2006;9(3):230-4
pubmed: 16683009
Mol Cancer Res. 2003 Aug;1(10):707-15
pubmed: 12939396
Endocr Rev. 2004 Apr;25(2):276-308
pubmed: 15082523
Endocr Rev. 2007 Dec;28(7):778-808
pubmed: 17940184
PLoS One. 2011;6(7):e21417
pubmed: 21789170
Cancer Res. 1997 Mar 15;57(6):1086-90
pubmed: 9067276
Nature. 2009 Feb 12;457(7231):910-4
pubmed: 19212411
J Urol. 2015 Feb;193(2):690-8
pubmed: 25132238
J Biol Chem. 1994 May 6;269(18):13115-23
pubmed: 8175737
Cancer Res. 2008 Jun 1;68(11):4447-54
pubmed: 18519708
Proc Natl Acad Sci U S A. 2018 Jun 26;115(26):6810-6815
pubmed: 29844167
Cancer Res. 2009 Mar 15;69(6):2305-13
pubmed: 19244107
Mol Cell. 2020 Sep 3;79(5):812-823.e4
pubmed: 32668201
Oncology. 2000 Nov;59(4):269-82
pubmed: 11096338
Mol Cell Biol. 2003 Dec;23(23):8563-75
pubmed: 14612401
Cancer Res. 2008 Aug 1;68(15):6407-15
pubmed: 18676866
Hum Mutat. 2010 Jan;31(1):74-80
pubmed: 19830810
Mol Cancer Res. 2017 Jan;15(1):59-68
pubmed: 27671337
Endocrinology. 2021 Mar 1;162(3):
pubmed: 33300995
Pharmacol Ther. 2013 Dec;140(3):223-38
pubmed: 23859952
J Clin Invest. 2014 Jan;124(1):398-412
pubmed: 24316975
Clin Cancer Res. 2019 Jun 15;25(12):3689-3701
pubmed: 30846479
J Steroid Biochem Mol Biol. 2016 Oct;163:121-8
pubmed: 27137100
Cancer Res. 2012 Jul 15;72(14):3457-62
pubmed: 22710436
Cancer Res. 2008 Jul 1;68(13):5469-77
pubmed: 18593950
Int J Cancer. 2002 Mar 1;98(1):19-22
pubmed: 11857379
J Clin Invest. 2010 Aug;120(8):2715-30
pubmed: 20644256
Nat Rev Urol. 2015 Mar;12(3):137-44
pubmed: 25666893
Int J Cancer. 2000 Oct 15;88(2):176-9
pubmed: 11004665
Mol Cell. 2018 Oct 18;72(2):341-354.e6
pubmed: 30270106
Oncotarget. 2015 Dec 15;6(40):42651-60
pubmed: 26315396