Gli Transcription Factors Mediate the Oncogenic Transformation of Prostate Basal Cells Induced by a Kras-Androgen Receptor Axis*
crossmark THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 291, NO. 49, pp. 25749–25760, December 2, 2016 © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A. Gli Transcription Factors Mediate the Oncogenic Transformation of Prostate Basal Cells Induced by a Kras-Androgen Receptor Axis*□S Received for publication, August 12, 2016, and in revised form, September 28, 2016 Published, JBC Papers in Press, October 19, 2016, DOI 10.1074/jbc.M116.753129 Meng Wu‡, Lishann Ingram‡, Ezequiel J. Tolosa§, Renzo E. Vera§, Qianjin Li‡, Sungjin Kim‡, Yongjie Ma‡, Demetri D. Spyropoulos¶, Zanna Beharryʈ, Jiaoti Huang**, Martin E. Fernandez-Zapico§, and Houjian Cai‡1 From the ‡Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia 30602, the §Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota 55905, the ¶Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, the ʈDepartment of Chemistry and Physics, Florida Gulf Coast University, Fort Myers, Florida 33965, and the **Department of Pathology, School of Medicine, Duke University, Durham, North Carolina 27710 Edited by Eric Fearon Although the differentiation of oncogenically transformed cer progression has been characterized with multiple stages, 2 basal progenitor cells is one of the key steps in prostate tumori- including benign, prostatic intraepithelial neoplasia (PIN), Downloaded from genesis, the mechanisms mediating this cellular process are still invasive adenocarcinoma, and metastatic cancer (2). Numerous ؉ largely unknown. Here we demonstrate that an expanded p63 oncogenic driver genes, including loss of tumor suppressors, ؉ and CK5 basal/progenitor cell population, induced by the con- overexpression, and/or activation of oncogenes, have been comitant activation of oncogenic Kras(G12D) and androgen identified based on genetic analysis of clinical prostate tumors.
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