Reactive oxygen species mediate androgen receptor- and serum starvation-elicited downstream signaling of ADAM9 expression in human prostate cancer cells
Article first published online: 6 MAR 2007
Copyright © 2007 Wiley-Liss, Inc.
Volume 67, Issue 7, pages 722–731, 15 May 2007
How to Cite
Shigemura, K., Sung, S.-Y., Kubo, H., Arnold, R. S., Fujisawa, M., Gotoh, A., Zhau, H. E. and Chung, L. W.K. (2007), Reactive oxygen species mediate androgen receptor- and serum starvation-elicited downstream signaling of ADAM9 expression in human prostate cancer cells. Prostate, 67: 722–731. doi: 10.1002/pros.20565
- Issue published online: 28 MAR 2007
- Article first published online: 6 MAR 2007
- Manuscript Accepted: 2 JAN 2007
- Manuscript Received: 30 AUG 2006
- NIH. Grant Numbers: 1PO1 CA098912, DAMD17-03-2-0033, PC0420260, 5P20GM072069, 1RO1 CA108468
- Georgia Cancer Coalition
- prostate cancer;
- androgen-independent progression;
- androgen receptor;
- serum deprivation;
- reactive oxygen species (ROS);
- signal transduction
The A Disintegrin And Metalloprotease (ADAM) family is a group of transmembrane proteins containing cell adhesive and proteolytic functional domains. ADAM9 expression was shown to be mediated by androgen receptor (AR) and stress conditions. This study determined a common mediator responsible for ADAM9 protein regulation which supports human prostate cancer (PCa) cell growth and survival.
ADAM9 protein expression was measured under androgen, anti-androgen, hydrogen peroxide, and/or serum starvation conditions in PCa cells. The roles of reactive oxygen species (ROS) were assessed in the presence or absence of recombinant catalase, or in cells stably transfected with either catalase- or a control neo-cDNA expression vector. ROS was assayed by dihydroethidium (DHE) followed by FACS analysis.
ADAM9 protein expression was upregulated by androgen in AR-positive but not in AR-negative PCa cells. The anti-androgen bicalutamide effectively blocked this induction. While serum starvation enhanced ADAM9 expression in AR-positive PCa cells, this stress condition did not alter ADAM9 expression in AR-negative PCa cells. Parallel results also showed that androgen treatment or serum starvation enhanced ROS only in AR-positive but not in AR-negative PCa cells. ROS appears to be a common downstream mediator of androgen- or serum starvation-induced ADAM9 expression since addition of hydrogen peroxide or introduction of catalase, either enhanced or abolished respectively ADAM9 protein expression by both AR-positive and -negative PCa cells.
These findings suggest that ROS is: a common mediator responsible for ADAM9 protein induction in human PCa cells, downstream from AR, and stress response signaling. Prostate 67: 722–731, 2007. © 2007 Wiley-Liss, Inc.