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Inhibition of ADAM9 expression induces epithelial phenotypic alterations and sensitizes human prostate cancer cells to radiation and chemotherapy

Authors

  • Sajni Josson,

    Corresponding author
    1. Uro-Oncology Research Program, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California
    • Uro-Oncology Research Program, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8750 Beverly blvd., Atrium 103, Los Angeles, CA 90048.
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  • Cynthia S. Anderson,

    1. Radiation Oncology, Emory University School of Medicine, Atlanta, Georgia
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  • Shian-Ying Sung,

    1. Graduate Institute of Cancer Biology, Center for Molecular Medicine, China Medical University & Hospital, Taichung, Taiwan
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  • Peter A.S. Johnstone,

    1. Radiation Oncology, Indiana University School of Medicine, Bloomington, Indiana
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  • Hiroyuki Kubo,

    1. Department of Urology, Kagoshima University, Kagoshima, Japan
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  • Chia-Ling Hsieh,

    1. Graduate Institute of Cancer Biology, Center for Molecular Medicine, China Medical University & Hospital, Taichung, Taiwan
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  • Rebecca Arnold,

    1. Molecular Urology Therapeutics, Emory University School of Medicine, Atlanta, Georgia
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  • Murali Gururajan,

    1. Uro-Oncology Research Program, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California
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  • Clayton Yates,

    1. Department of Biology, Center for Cancer Research, Tuskegee University, Alabama
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  • Leland W.K. Chung

    Corresponding author
    1. Uro-Oncology Research Program, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California
    • Uro-Oncology Research Program, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8750 Beverly blvd., Atrium 103, Los Angeles, CA 90048.
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  • Sajni Josson and Cynthia S. Anderson contributed equally to this work.

Abstract

INTRODUCTION

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.

RESULTS

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.

CONCLUSIONS

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.

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