STAT5A/B Blockade Sensitizes Prostate Cancer to Radiation through Inhibition of RAD51 and DNA Repair

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Cristina MarantoMarja T Nevalainen

Abstract

Purpose: The standard treatment for organ-confined prostate cancer is surgery or radiation, and locally advanced prostate cancer is typically treated with radiotherapy alone or in combination with androgen deprivation therapy. Here, we investigated whether Stat5a/b participates in regulation of double-strand DNA break repair in prostate cancer, and whether Stat5 inhibition may provide a novel strategy to sensitize prostate cancer to radiotherapy.Experimental Design: Stat5a/b regulation of DNA repair in prostate cancer was evaluated by comet and clonogenic survival assays, followed by assays specific to homologous recombination (HR) DNA repair and nonhomologous end joining (NHEJ) DNA repair. For HR DNA repair, Stat5a/b regulation of Rad51 and the mechanisms underlying the regulation were investigated in prostate cancer cells, xenograft tumors, and patient-derived prostate cancers ex vivo in 3D explant cultures. Stat5a/b induction of Rad51 and HR DNA repair and responsiveness to radiation were evaluated in vivo in mice bearing prostate cancer xenograft tumors.Results: Stat5a/b is critical for Rad51 expression in prostate cancer via Jak2-dependent mechanisms by inducing Rad51 mRNA levels. Consistent with this, genetic knockdown of...Continue Reading

References

Feb 1, 1995·Mutation Research·D W FairbairnK L O'Neill
Oct 29, 1999·Genes & Development·A J PierceM Jasin
Mar 10, 2001·Molecular Cell·M E MoynahanM Jasin
Oct 31, 2001·Molecular Cell·A SlupianekT Skorski
Sep 5, 2002·Nature Reviews. Molecular Cell Biology·David E Levy, J E Darnell
Apr 30, 2003·The Journal of Biological Chemistry·Tommi J AhonenMarja T Nevalainen
Oct 29, 2004·Nature Reviews. Cancer·Nicholas TurnerAlan Ashworth
Aug 24, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hongzhen LiMarja T Nevalainen
Nov 15, 2007·The Journal of Biological Chemistry·Michael R Lieber
Jan 4, 2008·Cancer Research·Shyh-Han TanMarja T Nevalainen
Feb 8, 2008·Nature Reviews. Cancer·Thomas HelledayRicky A Sharma
Mar 5, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ayush DagvadorjMarja T Nevalainen
Oct 3, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ayush DagvadorjMarja T Nevalainen
Dec 25, 2008·Proceedings of the National Academy of Sciences of the United States of America·Christopher M HineVera Gorbunova
Dec 17, 2009·Histopathology·Anita MitraChristopher S Foster
Jan 12, 2010·Nature Reviews. Urology·Seth A Rosenthal, Howard M Sandler
May 11, 2013·The American Journal of Pathology·Bassem R HaddadMarja T Nevalainen
Aug 15, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lei GuMarja T Nevalainen
Sep 5, 2013·Cold Spring Harbor Perspectives in Biology·Alexandre Maréchal, Lee Zou
Oct 8, 2013·Cold Spring Harbor Perspectives in Biology·Maria Jasin, Rodney Rothstein
May 21, 2014·Nature Reviews. Clinical Oncology·Albert J ChangHoward I Scher
Jun 21, 2014·Future Oncology·Mark R KelleyMelissa L Fishel
Oct 30, 2014·The New England Journal of Medicine·Donal P McLornanGhulam J Mufti
Mar 18, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Clare L ScottScott H Kaufmann
Apr 3, 2015·Cold Spring Harbor Perspectives in Biology·Rohit PrakashMaria Jasin
Jun 16, 2015·Lancet·Gerhardt AttardJohann S de Bono
Sep 13, 2015·The American Journal of Pathology·Pooja G TalatiMarja T Nevalainen
Jan 19, 2016·Nature Reviews. Cancer·Christopher J Lord, Alan Ashworth
Oct 30, 2016·European Urology·Joaquin MateoJohann S de Bono

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Citations

Mar 21, 2018·Nature Reviews. Urology·Clemens Thoma
Apr 15, 2020·Cellular and Molecular Life Sciences : CMLS·D ContarteseM Fini
Nov 30, 2018·Journal of Cellular Biochemistry·Hongyu LiYunshan Wang
Mar 3, 2020·Cancer Immunology, Immunotherapy : CII·Diane L Costanzo-GarveyLeah M Cook
Feb 1, 2020·Pharmacology & Therapeutics·Erik LauriniSabrina Pricl
Jan 29, 2021·International Journal of Radiation Oncology, Biology, Physics·Yin YuanHonggang Wang
Apr 10, 2021·Current Research in Translational Medicine·Liang WangHaibo Xu
May 1, 2021·Journal of Clinical Medicine·Annika ReddigDirk Reinhold
Oct 29, 2020·Seminars in Cell & Developmental Biology·Ödül Karayazi AtıcıCarrie S Shemanko
Jun 10, 2021·Clinical Epigenetics·Catarina Macedo-SilvaLucia Altucci
Aug 22, 2020·The International Journal of Biochemistry & Cell Biology·William A HallMarja T Nevalainen

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