Sajni Josson and Cynthia S. Anderson contributed equally to this work.
Inhibition of ADAM9 expression induces epithelial phenotypic alterations and sensitizes human prostate cancer cells to radiation and chemotherapy†
Article first published online: 29 JUL 2010
Copyright © 2010 Wiley-Liss, Inc.
Volume 71, Issue 3, pages 232–240, 15 February 2011
How to Cite
Josson, S., Anderson, C. S., Sung, S.-Y., Johnstone, P. A.S., Kubo, H., Hsieh, C.-L., Arnold, R., Gururajan, M., Yates, C. and Chung, L. W.K. (2011), Inhibition of ADAM9 expression induces epithelial phenotypic alterations and sensitizes human prostate cancer cells to radiation and chemotherapy. Prostate, 71: 232–240. doi: 10.1002/pros.21237
- Issue published online: 20 JAN 2011
- Article first published online: 29 JUL 2010
- Manuscript Accepted: 18 JUN 2010
- Manuscript Received: 19 JAN 2010
- NSC. Grant Numbers: 2P01CA098912, 1RO1CA122602, 96-2320-B-039-033-MY3
- prostate cancer;
Recent studies demonstrated the importance of ADAM9 in prostate cancer relapse upon therapy. In this study, we determined the role of ADAM9 in the therapeutic resistance to radiation and chemotherapy.
MATERIALS AND METHODS
ADAM9 was either transiently or stably knocked down in C4-2 prostate cancer cells. The sensitivity of ADAM9 knockdown cells toward radiation and chemotherapeutic agents were determined. Additionally, the effects of ADAM9 knockdown on prostate cancer cell morphology, biochemical and functional alterations were accessed.
Both transient and stable knockdown of ADAM9 resulted in increased apoptosis and increased sensitivity to radiation. ADAM9 knockdown also increased prostate cancer sensitivity to several chemotherapeutic drugs. ADAM9 knockdown resulted in increased E-cadherin and altered integrin expression and underwent phenotypic epithelial transition. These were reflected by the morphological, biochemical, and functional alterations in the ADAM9 knockdown cells.
ADAM9 plays a crucial role in prostate cancer progression and therapeutic resistance in part by altering E-cadherin and integrin expression. ADAM9 is an important target for the consideration of treating prostate cancer patients who developed therapeutic resistance and disease relapse. Prostate 71:232–240, 2011. © 2010 Wiley-Liss, Inc.