| Enhanced expression of Annexin A4 in clear cell carcinoma of the ovary and its association with chemoresistance to carboplatin. | |
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MedLine Citation:
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PMID: 19598262 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Clear cell carcinoma (CCC) of the ovary is known to be highly resistant to platinum-based chemotherapy. The purpose of our study was to identify a candidate protein that is associated with chemoresistance of CCC and to investigate the specific mechanism of chemoresistance conferred by the identified protein. Enhanced expression of Annexin A4 (Anx A4) was identified in ovarian CCC cells using 2-D differential gel electrophoresis (2D-DIGE) and mass spectrometry. Anx A4 levels were elevated in CCC cells compared with non-CCC cells as determined by real-time RT-PCR and Western blot analysis. Immunohistochemical analysis of Anx A4 was performed in 126 epithelial ovarian cancer tissue samples and demonstrated significantly elevated levels of Anx A4 protein levels in ovarian CCC tumors compared with ovarian serous and endometrioid tumors (p < 0.01). Anx A4-transfected ovarian non-CCC cells were more resistant to carboplatin (IC50 = 42 microM) compared with control cells (IC50 = 23 microM) as determined by modified MTT assay. Intracellular platinum levels were significantly lower in Anx A4-transfected cells compared with control cells after carboplatin treatment (p = 0.0020) and after an additional 360 min of carboplatin-free incubation (p = 0.0004), as measured by atomic absorption spectrophotometry. Expression of Anx A4 is elevated in ovarian CCC tumors and is associated with chemoresistance in cultured ovarian cancer cells. These results demonstrate that Anx A4 confers chemoresistance in ovarian cancer cells in part by enhancing drug efflux. Thus, Anx A4 may represent a novel therapeutic target of chemoresistance in patients with ovarian CCC. |
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Authors:
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Ayako Kim; Takayuki Enomoto; Satoshi Serada; Yutaka Ueda; Tsuyoshi Takahashi; Barry Ripley; Takashi Miyatake; Masami Fujita; Chun Man Lee; Koji Morimoto; Minoru Fujimoto; Tadashi Kimura; Tetsuji Naka |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: International journal of cancer. Journal international du cancer Volume: 125 ISSN: 1097-0215 ISO Abbreviation: Int. J. Cancer Publication Date: 2009 Nov |
Date Detail:
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Created Date: 2009-09-28 Completed Date: 2009-11-05 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: United States |
Other Details:
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Languages: eng Pagination: 2316-22 Citation Subset: IM |
Affiliation:
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Department of Obstetrics and Gynaecology, Osaka University Graduate School of Medicine, Osaka, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenocarcinoma, Clear Cell
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drug therapy,
metabolism*,
pathology Adult Aged Aged, 80 and over Annexin A4 / metabolism* Antineoplastic Agents / therapeutic use* Blotting, Western Carboplatin / therapeutic use* Drug Resistance, Neoplasm* Electrophoresis, Gel, Two-Dimensional Female Humans Immunoenzyme Techniques Middle Aged Ovarian Neoplasms / drug therapy, metabolism*, pathology Prognosis RNA, Messenger / genetics, metabolism Reverse Transcriptase Polymerase Chain Reaction Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Survival Rate Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/Annexin A4; 0/Antineoplastic Agents; 0/RNA, Messenger; 41575-94-4/Carboplatin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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