TY - JOUR
T1 - Suppression of annexin A11 in ovarian cancer
T2 - Implications in chemoresistance
AU - Song, Jin
AU - Shih, Ie Ming
AU - Chan, Daniel W.
AU - Zhang, Zhen
N1 - Funding Information:
Abbreviations: RNAi, RNA interference; siRNA, small interfering RNA; IHC, immunohistochemistry; EDR, extreme drug resistance assay Address all correspondence to: Zhen Zhang, Department of Pathology, Johns Hopkins Medical Institutions, 1550 Orleans St, Baltimore, MD 21231. E-mail: zzhang7@jhmi.edu 1This research was partially supported by a Department of Defense IDEA grant DAMD17-OC03-IDEA, a National Institutes of Health/National Cancer Institute Early Detection Research Network grant CA115102-01, and National Institutes of Health/ National Cancer Institute grants 1P50 CA83639, CA129080, and CA103937. 2This article refers to supplementary materials, which are designated by Tables W1 and W2 and are available online at www.neoplasia.com. Received 5 February 2009; Revised 31 March 2009; Accepted 2 April 2009 Copyright © 2009 Neoplasia Press, Inc. All rights reserved 1522-8002/09/$25.00 DOI 10.1593/neo.09286
PY - 2009/6
Y1 - 2009/6
N2 - Ovarian cancer patients treated with cisplatin-based chemotherapy often develop acquired cisplatin resistance and, consequently, cancer recurrence. We have previously reported that annexin A11 is associated with cisplatin resistance and related to tumor recurrence in ovarian cancer patients. In this study, we used small interfering RNA to suppress annexin A11 expression in ovarian cancer cells followed by various in vitro assays. We showed that knockdown of annexin A11 expression reduced cell proliferation and colony formation ability of ovarian cancer cells. Epigenetic silencing of annexin A11 conferred cisplatin resistance to ovarian cancer cells. Through a comprehensive time course study of cisplatin response in ovarian cancer cells with/without suppression of annexin A11 expression using whole-genome oligonucleotide microarrays, we identified a set of differentially expressed genes associated with annexin A11 expression and some patterns of gene expressions in response to cisplatin exposure. These identified genes/patterns were further validated by real-time polymerase chain reaction and immunoblot analysis. Many of them such as HMOX1, TGFBI, LY6D, S100P, EIF4EBP2, DHRS2, and PCSK9 have been involved in apoptosis, cell cycling/proliferation, cell adhesion/migration, transcription regulation, and signal transduction. In addition, immunohistochemistry analyses indicated that annexin A11 immunointensity inversely correlated with HMOX1 immunoreactivity in 142 ovarian cancer patients. In contrast to annexin A11, HMOX1 immunoreactivity positively correlated with in vitro cisplatin resistance in ovarian cancers. Collectively, annexin A11 is directly involved in cell proliferation and cisplatin resistance of ovarian cancer. Manipulation of annexin A11 and its associated genes may represent a novel therapeutic strategy in human ovarian cancers.
AB - Ovarian cancer patients treated with cisplatin-based chemotherapy often develop acquired cisplatin resistance and, consequently, cancer recurrence. We have previously reported that annexin A11 is associated with cisplatin resistance and related to tumor recurrence in ovarian cancer patients. In this study, we used small interfering RNA to suppress annexin A11 expression in ovarian cancer cells followed by various in vitro assays. We showed that knockdown of annexin A11 expression reduced cell proliferation and colony formation ability of ovarian cancer cells. Epigenetic silencing of annexin A11 conferred cisplatin resistance to ovarian cancer cells. Through a comprehensive time course study of cisplatin response in ovarian cancer cells with/without suppression of annexin A11 expression using whole-genome oligonucleotide microarrays, we identified a set of differentially expressed genes associated with annexin A11 expression and some patterns of gene expressions in response to cisplatin exposure. These identified genes/patterns were further validated by real-time polymerase chain reaction and immunoblot analysis. Many of them such as HMOX1, TGFBI, LY6D, S100P, EIF4EBP2, DHRS2, and PCSK9 have been involved in apoptosis, cell cycling/proliferation, cell adhesion/migration, transcription regulation, and signal transduction. In addition, immunohistochemistry analyses indicated that annexin A11 immunointensity inversely correlated with HMOX1 immunoreactivity in 142 ovarian cancer patients. In contrast to annexin A11, HMOX1 immunoreactivity positively correlated with in vitro cisplatin resistance in ovarian cancers. Collectively, annexin A11 is directly involved in cell proliferation and cisplatin resistance of ovarian cancer. Manipulation of annexin A11 and its associated genes may represent a novel therapeutic strategy in human ovarian cancers.
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U2 - 10.1593/neo.09286
DO - 10.1593/neo.09286
M3 - Article
C2 - 19484149
AN - SCOPUS:66449117372
VL - 11
SP - 605
EP - 614
JO - Neoplasia
JF - Neoplasia
SN - 1522-8002
IS - 6
ER -