ERG/AKR1C3/AR Constitutes a Feed-Forward Loop for AR Signaling in Prostate Cancer Cells

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Katelyn PowellSreenivasa R Chinni

Abstract

Intratumoral androgen synthesis in prostate cancer contributes to the development of castration-resistant prostate cancer (CRPC). Several enzymes responsible for androgen biosynthesis have been shown to be overexpressed in CRPC, thus contributing to CRPC in a castrated environment. The TMPRSS2-ERG transcription factor has been shown to be present in primary prostate cancer tumors as well as CRPC tumors. We hypothesize that TMPRSS2-ERG fusions regulate androgen biosynthetic enzyme (ABE) gene expression and the production of androgens, which contributes to the development of CRPC. We used a panel of assays, including lentivirus transduction, gene expression, chromatin immunoprecipitation and sequencing, liquid chromatography-mass spectrometric quantitation, immunocytochemistry, immunohistochemistry, and bioinformatics analysis of gene microarray databases, to determine ERG regulation of androgen synthesis. We found that ERG regulated the expression of the ABE AKR1C3 in prostate cancer cells via direct binding to the AKR1C3 gene. Knockdown of ERG resulted in reduced AKR1C3 expression, which caused a reduction in both DHT synthesis and PSA expression in VCaP prostate cancer cells treated with 5α-androstanedione (5α-Adione), a DHT p...Continue Reading

References

Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Oct 29, 2005·Science·Scott A TomlinsArul M Chinnaiyan
Mar 6, 2007·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Rohit MehraRajal B Shah
Jul 20, 2007·Oncogene·G AttardUNKNOWN Transatlantic Prostate Group
Feb 20, 2008·Neoplasia : an International Journal for Oncology Research·Scott A TomlinsArul M Chinnaiyan
May 27, 2008·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Maisa YoshimotoJeremy A Squire
May 29, 2008·Journal of the National Cancer Institute·Sunita R SetlurMark A Rubin
Dec 23, 2008·Molecular and Cellular Endocrinology·Krishan K RasiahVanessa M Hayes
Apr 28, 2009·Nature Genetics·Jennifer C KingCharles L Sawyers
May 2, 2009·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Bo HanRajal B Shah
Dec 21, 2010·Neoplasia : an International Journal for Oncology Research·David S RickmanFrancesca Demichelis
May 27, 2011·The New England Journal of Medicine·Johann S de BonoUNKNOWN COU-AA-301 Investigators
Jun 28, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·James L MohlerElizabeth M Wilson
Jul 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Kai-Hsiung ChangNima Sharifi
Dec 21, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Eleni EfstathiouChristopher J Logothetis
Dec 12, 2012·The New England Journal of Medicine·Charles J RyanUNKNOWN COU-AA-302 Investigators
Jun 12, 2013·The Journal of Steroid Biochemistry and Molecular Biology·Adegoke O AdenijiTrevor M Penning
Aug 7, 2013·Molecular Cancer Research : MCR·Rajareddy SingareddySreenivasa R Chinni

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Citations

Aug 25, 2015·Seminars in Cancer Biology·Frédéric R SanterRhiannon V McNeill
Mar 14, 2017·Scientific Reports·Kai LiYong Xu
May 19, 2018·Endocrine-related Cancer·Matias KnuuttilaMatti Poutanen
Aug 24, 2018·Endocrine Reviews·Trevor M PenningRichard J Auchus
Mar 28, 2019·Journal of Molecular Endocrinology·Matias KnuuttilaMatti Poutanen
Aug 5, 2017·Cancer Science·Toshiro MigitaSatoshi Inoue
Apr 28, 2016·Current Opinion in Endocrinology, Diabetes, and Obesity·Trevor M Penning, Daniel Tamae
Sep 10, 2020·Journal of Cellular and Molecular Medicine·Bin WangKaijie Wu
Apr 30, 2017·Nature Reviews. Cancer·Gina M SizemoreMichael C Ostrowski
Jul 25, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Charles DaiNima Sharifi
Feb 19, 2019·Asian Journal of Urology·Liang DongKenneth J Pienta
Nov 2, 2019·The Journal of Steroid Biochemistry and Molecular Biology·Monique BarnardKarl-Heinz Storbeck
Oct 16, 2019·The Journal of Steroid Biochemistry and Molecular Biology·Trevor M Penning, Andrea J Detlefsen
Jan 2, 2021·The Journal of Biological Chemistry·Irfan AsanganiTrevor M Penning
Jan 12, 2021·The Journal of Biological Chemistry·Irfan AsanganiTrevor M Penning
Jul 28, 2021·Pharmacological Reviews·Trevor M PenningTea Lanišnik Rižner
May 29, 2020·Journal of Medicinal Chemistry·Yang LiuHaopeng Sun
Aug 24, 2021·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Richard J Epstein

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