Int J Biol Sci 2014; 10(6):620-626. doi:10.7150/ijbs.8264 This issue Cite

Review

Androgen Receptor Activation in Castration-Recurrent Prostate Cancer: The Role of Src-Family and Ack1 Tyrosine Kinases

Irwin H. Gelman

Department of Cancer Genetics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.

Citation:
Gelman IH. Androgen Receptor Activation in Castration-Recurrent Prostate Cancer: The Role of Src-Family and Ack1 Tyrosine Kinases. Int J Biol Sci 2014; 10(6):620-626. doi:10.7150/ijbs.8264. https://www.ijbs.com/v10p0620.htm
Other styles

File import instruction

Abstract

There is growing appreciation that castration-recurrent prostate cancer (CR-CaP) is driven by the continued expression of androgen receptor (AR). AR activation in CR-CaP through various mechanisms, including AR overexpression, expression of AR splice variants or mutants, increased expression of co-regulator proteins, and by post-translational modification, allows for the induction of AR-regulated genes in response to very low levels of tissue-expressed, so-called intracrine androgens, resulting in pathways that mediate CaP proliferation, anti-apoptosis and oncogenic aggressiveness. The current review focuses on the role played by Src-family (SFK) and Ack1 non-receptor tyrosine kinases in activating AR through direct phosphorylation, respectively, on tyrosines 534 or 267, and how these modifications facilitate progression to CR-CaP. The fact that SFK and Ack1 are central mediators for multiple growth factor receptor signaling pathways that become activated in CR-CaP, especially in the context of metastatic growth in the bone, has contributed to recent therapeutic trials using SFK/Ack1 inhibitors in monotherapy or in combination with antagonists of the AR activation axis.

Keywords: Src-family tyrosine kinases, Ack1, androgen receptor, prostate cancer, castration-recurrence.


Citation styles

APA
Gelman, I.H. (2014). Androgen Receptor Activation in Castration-Recurrent Prostate Cancer: The Role of Src-Family and Ack1 Tyrosine Kinases. International Journal of Biological Sciences, 10(6), 620-626. https://doi.org/10.7150/ijbs.8264.

ACS
Gelman, I.H. Androgen Receptor Activation in Castration-Recurrent Prostate Cancer: The Role of Src-Family and Ack1 Tyrosine Kinases. Int. J. Biol. Sci. 2014, 10 (6), 620-626. DOI: 10.7150/ijbs.8264.

NLM
Gelman IH. Androgen Receptor Activation in Castration-Recurrent Prostate Cancer: The Role of Src-Family and Ack1 Tyrosine Kinases. Int J Biol Sci 2014; 10(6):620-626. doi:10.7150/ijbs.8264. https://www.ijbs.com/v10p0620.htm

CSE
Gelman IH. 2014. Androgen Receptor Activation in Castration-Recurrent Prostate Cancer: The Role of Src-Family and Ack1 Tyrosine Kinases. Int J Biol Sci. 10(6):620-626.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
Popup Image