Effect of Ack1 tyrosine kinase inhibitor on ligand-independent androgen receptor activity.

The Prostate
Kiran MahajanNupam P Mahajan

Abstract

Androgen receptor (AR) plays a critical role in the progression of both androgen-dependent and androgen-independent prostate cancer (AIPC). Ligand-independent activation of AR in AIPC or castration resistant prostate cancer (CRPC) is often associated with poor prognosis. Recently, tyrosine kinase Ack1 has been shown to regulate AR activity by phosphorylating it at tyrosine 267 and this event was shown to be critical for AIPC growth. However, whether a small molecule inhibitor that can mitigate Ack1 activation is sufficient to abrogate AR activity on AR regulated promoters in androgen-depleted environment is not known. We have generated two key resources, antibodies that specifically recognize pTyr267-AR and synthesized a small molecule inhibitor of Ack1, 4-amino-5,6-biaryl-furo[2,3-d]pyrimidine (named here as AIM-100) to test whether AIM-100 modulates ligand-independent AR activity and inhibits prostate cell growth. Prostate tissue microarray analysis indicates that Ack1 Tyr284 phosphorylation correlates positively with disease progression and negatively with the survival of prostate cancer patients. Interestingly, neither pTyr267-AR expression nor its transcriptional activation was affected by anti-androgens in activated Ack1 ...Continue Reading

References

May 25, 1995·The New England Journal of Medicine·M E TaplinS P Balk
Nov 22, 2001·Journal of the National Cancer Institute·M E GrossmannD J Tindall
May 17, 2002·The Journal of Biological Chemistry·Daniel GioeliMichael J Weber
Jan 2, 2004·Nature Medicine·Charlie D ChenCharles L Sawyers
Jan 22, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·C M CanilL Seymour
Jun 25, 2005·Journal of Medicinal Chemistry·Nicolas FoloppeAllan E Surgenor
Jul 15, 2005·The New England Journal of Medicine·Daniela S Krause, Richard A Van Etten
Oct 26, 2005·Proceedings of the National Academy of Sciences of the United States of America·Edward Htun van der HorstScott Powers
Nov 10, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Howard I Scher, Charles L Sawyers
Jun 17, 2006·Proceedings of the National Academy of Sciences of the United States of America·Maria L GalisteoJoseph Schlessinger
Oct 14, 2006·The Journal of Biological Chemistry·Katarzyna ModzelewskaPatricia J Keely
May 15, 2007·Proceedings of the National Academy of Sciences of the United States of America·Nupam P MahajanYoung E Whang
Sep 8, 2007·BJU International·Eric J SmallFairooz F Kabbinavar
May 10, 2008·Annals of Oncology : Official Journal of the European Society for Medical Oncology·G GravisP Viens
Jun 30, 2009·The Prostate·Claudio FestucciaVincenzo Tombolini
Mar 25, 2010·PloS One·Kiran MahajanNupam P Mahajan

❮ Previous
Next ❯

Citations

Jun 4, 2011·Journal of Signal Transduction·Victoria Prieto-Echagüe, W Todd Miller
Mar 26, 2011·Molecular Endocrinology·Kristin R Lamont, Donald J Tindall
Mar 25, 2010·PloS One·Kiran MahajanNupam P Mahajan
Jul 19, 2013·International Journal of Molecular Sciences·Travis van der SteenHaojie Huang
Dec 16, 2011·Future Medicinal Chemistry·Gary E GallickSue-Hwa Lin
Jan 5, 2014·Cancer Metastasis Reviews·Zoran Culig, Frédéric R Santer
Apr 20, 2013·Cancer Letters·Kiran Mahajan, Nupam P Mahajan
Oct 22, 2014·Cancer Metastasis Reviews·Anait S LevensonXu Zhang
Dec 2, 2015·Proceedings of the National Academy of Sciences of the United States of America·Sijia WuHaley E Melikian
Mar 6, 2016·Trends in Endocrinology and Metabolism : TEM·Matthew J Schiewer, Karen E Knudsen
Nov 8, 2015·Nucleic Acids Research·Kiran Mahajan, Nupam P Mahajan
Nov 2, 2013·Journal of Surgical Oncology·Kazuya ShinmuraHaruhiko Sugimura
Feb 11, 2012·The American Journal of Pathology·Kiran MahajanNupam P Mahajan
Dec 23, 2015·International Journal of Molecular Sciences·Jing-Wen ShihChia-Ling Hsieh
Mar 30, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Xing-Hua XiaoLi-Xia Xiong
Aug 26, 2014·The Journal of Biological Chemistry·Kiran MahajanNupam P Mahajan
Feb 2, 2018·Scientific Reports·Nupam P MahajanKiran Mahajan
May 1, 2010·Journal of Cellular Physiology·Kiran Mahajan, Nupam P Mahajan
Nov 28, 2019·BioMed Research International·Xia LiuBaolin Han

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.