Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2009-9-28
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1097-0215
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
125
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2316-22
pubmed:meshHeading
pubmed-meshheading:19598262-Adenocarcinoma, Clear Cell, pubmed-meshheading:19598262-Adult, pubmed-meshheading:19598262-Aged, pubmed-meshheading:19598262-Aged, 80 and over, pubmed-meshheading:19598262-Annexin A4, pubmed-meshheading:19598262-Antineoplastic Agents, pubmed-meshheading:19598262-Blotting, Western, pubmed-meshheading:19598262-Carboplatin, pubmed-meshheading:19598262-Drug Resistance, Neoplasm, pubmed-meshheading:19598262-Electrophoresis, Gel, Two-Dimensional, pubmed-meshheading:19598262-Female, pubmed-meshheading:19598262-Humans, pubmed-meshheading:19598262-Immunoenzyme Techniques, pubmed-meshheading:19598262-Middle Aged, pubmed-meshheading:19598262-Ovarian Neoplasms, pubmed-meshheading:19598262-Prognosis, pubmed-meshheading:19598262-RNA, Messenger, pubmed-meshheading:19598262-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:19598262-Spectrometry, Mass, Matrix-Assisted Laser..., pubmed-meshheading:19598262-Survival Rate, pubmed-meshheading:19598262-Tumor Cells, Cultured
pubmed:year
2009
pubmed:articleTitle
Enhanced expression of Annexin A4 in clear cell carcinoma of the ovary and its association with chemoresistance to carboplatin.
pubmed:affiliation
Department of Obstetrics and Gynaecology, Osaka University Graduate School of Medicine, Osaka, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't