2017 Fiscal Year Final Research Report
The investigation of new treatment for ovarian clear cell carcinoma with TOP2A amplification
| Project/Area Number |
16H06907
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2016-08-26 – 2018-03-31
|
| Keywords | 卵巣明細胞癌 / 染色体17番長腕増幅 / シスプラチン耐性 / PDK2 |
|---|
| Outline of Final Research Achievements |
Ovarian clear cell carcinoma (CCC) has poor prognosis owing to its chemoresistance. Here we aimed to identify a biomarker of this drug resistance and the therapeutic target of CCC. Whole exome sequencing and expression microarray were conducted using 39 CCC clinical samples and 13 CCC cell lines. IC50 values and apoptosis of 13 CCC cell lines against cisplatin were measured by cleaved caspase-3. Chr17q21-24 amplification correlated positively with IC50 values for cisplatin in 13 CCC cell lines (r>0.4). The expression levels of 59 genes located on chr17q21-24 are positively correlated with Chr17q21-24 amplification in 13 CCC cell lines and 18 CCC patients (r>0.4). Of these 59 genes, we focused on pyruvate dehydrogenase kinase isoform 2(PDK2). A PDK inhibitor and suppression of PDK2 decreased the IC50 values for cisplatin by increasing cleaved caspase-3 expression. PDK2 inhibition is a promising therapeutic strategy against CCC.
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| Free Research Field |
卵巣癌
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