TY - JOUR
T1 - Role of transcriptional corepressor CtBP1 in prostate cancer progression
AU - Wang, Rui
AU - Asangani, Irfan A.
AU - Chakravarthi, Balabhadrapatruni V.S.K.
AU - Ateeq, Bushra
AU - Lonigro, Robert J.
AU - Cao, Qi
AU - Mani, Ram Shankar
AU - Camacho, Daniel F.
AU - McGregor, Natalie
AU - Schumann, Taibriana E.W.
AU - Jing, Xiaojun
AU - Menawat, Radhika
AU - Tomlins, Scott A.
AU - Zheng, Heng
AU - Otte, Arie P.
AU - Mehra, Rohit
AU - Siddiqui, Javed
AU - Dhanasekaran, Saravana M.
AU - Nyati, Mukesh K.
AU - Pienta, Kenneth J.
AU - Palanisamy, Nallasivam
AU - Kunju, Lakshmi P.
AU - Rubin, Mark A.
AU - Chinnaiyan, Arul M.
AU - Varambally, Sooryanarayana
N1 - Funding Information:
Abbreviations: PCa, prostate cancer; CtBP1, C-terminal binding protein 1; HDAC, histone deacetylase; siRNA, small interfering RNA Address all correspondence to: Sooryanarayana Varambally, PhD, Michigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, 2900 Huron Parkway, Traverwood IV, Suite 100, Ann Arbor, MI 48109-0602. E-mail: [email protected] 1Research reported in this publication was supported in part by grants from the Department of Defense to A.M.C. (PC020322) and the National Cancer Institute of the National Institutes of Health to S.V. (R01CA154980). S.V. is also supported by a grant from the National Cancer Institute of the National Institutes of Health (R01CA157845). This work was also supported in part by the Prostate Cancer Foundation (A.M.C.), NIH Prostate Specialized Program of Research Excellence P50CA69568, and Early Detection Research Network UO1 CA111275 (A.M.C.). A.M.C. is also supported by the Doris Duke Charitable Foundation Clinical Scientist Award and the Howard Hughes Medical Institute. A.M.C. is an American Cancer Society Research Professor and a Taubman Scholar of the University of Michigan. 2This article refers to supplementary materials, which are designated by Table W1 and Figures W1 to W4 and are available online at www.neoplasia.com. 3Share senior authorship. Received 23 July 2012; Revised 22 August 2012; Accepted 24 August 2012 Copyright © 2012 Neoplasia Press, Inc. All rights reserved 1522-8002/12/$25.00 DOI 10.1593/neo.121192
PY - 2012/10
Y1 - 2012/10
N2 - Transcriptional repressors and corepressors play a critical role in cellular homeostasis and are frequently altered in cancer. C-terminal binding protein 1 (CtBP1), a transcriptional corepressor that regulates the expression of tumor suppressors and genes involved in cell death, is known to play a role in multiple cancers. In this study, we observed the overexpression and mislocalization of CtBP1 in metastatic prostate cancer and demonstrated the functional significance of CtBP1 in prostate cancer progression. Transient and stable knockdown of CtBP1 in prostate cancer cells inhibited their proliferation and invasion. Expression profiling studies of prostate cancer cell lines revealed that multiple tumor suppressor genes are repressed by CtBP1. Furthermore, our studies indicate a role for CtBP1 in conferring radiation resistance to prostate cancer cell lines. In vivo studies using chicken chorioallantoic membrane assay, xenograft studies, and murine metastasis models suggested a role for CtBP1 in prostate tumor growth and metastasis. Taken together, our studies demonstrated that dysregulated expression of CtBP1 plays an important role in prostate cancer progression and may serve as a viable therapeutic target.
AB - Transcriptional repressors and corepressors play a critical role in cellular homeostasis and are frequently altered in cancer. C-terminal binding protein 1 (CtBP1), a transcriptional corepressor that regulates the expression of tumor suppressors and genes involved in cell death, is known to play a role in multiple cancers. In this study, we observed the overexpression and mislocalization of CtBP1 in metastatic prostate cancer and demonstrated the functional significance of CtBP1 in prostate cancer progression. Transient and stable knockdown of CtBP1 in prostate cancer cells inhibited their proliferation and invasion. Expression profiling studies of prostate cancer cell lines revealed that multiple tumor suppressor genes are repressed by CtBP1. Furthermore, our studies indicate a role for CtBP1 in conferring radiation resistance to prostate cancer cell lines. In vivo studies using chicken chorioallantoic membrane assay, xenograft studies, and murine metastasis models suggested a role for CtBP1 in prostate tumor growth and metastasis. Taken together, our studies demonstrated that dysregulated expression of CtBP1 plays an important role in prostate cancer progression and may serve as a viable therapeutic target.
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U2 - 10.1593/neo.121192
DO - 10.1593/neo.121192
M3 - Article
C2 - 23097625
AN - SCOPUS:84867760327
SN - 1522-8002
VL - 14
SP - 905
EP - 914
JO - Neoplasia (United States)
JF - Neoplasia (United States)
IS - 10
ER -