2014 Fiscal Year Final Research Report
A new therapeutic target of uterine leiomyosarcoma identified by Isobaric Tags for Relative and Absolute Quantitation (iTRAQ).
| Project/Area Number |
25861491
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Keywords | 婦人科腫瘍 / 子宮平滑筋肉腫 / プラチナ耐性 / プラチナトランスポーター |
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| Outline of Final Research Achievements |
In this study, we investigated the role of ATP7A and ATP7B in uterine leiomyosarcoma (LMS) cells which had high level expression of ATP7A and ATP7B. In LMS cell lines, knockdown the expression of ATP7A and ATP7B improved the sensitivity of Cisplatin in vitro. Compared with control LMS cells, knockdown of ATP7A and ATP7B induced roughly 4-fold greater chemosensitization to Cisplatin (IC50: 17.0 μM to 6.1 μM, 4.3 μM respectively; p<0.01) To elucidate the mechanism underlying platinum resistance induced by ATP7A and ATP7B, intracellular platinum accumulation of LMS control cells, LMS silencing ATP7A cells and ATP7B cells after Cisplatin exposure were analyzed. Significantly increased platinum had accumulated in LMS silencing ATP7A and ATP7B cells compared with LMS control cells (p < 0.01). Thus, intracellular platinum accumulation was increased in LMS silencing ATP7A cells and ATP7B cells. To perform further investigation, we generate stable ATP7A and ATP7B knockdown cell lines.
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| Free Research Field |
医歯薬学
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