Transcriptional upregulation of HNF-1beta by NF-kB in ovarian clear cell carcinoma modulates susceptibility to apoptosis through alteration in bcl-2 expression
| Project/Area Number |
25670179
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Human pathology
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
Saegusa Makoto 北里大学, 医学部, 教授 (00265711)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | HNF-1beta / NF-kB / 卵巣明細胞癌 / bcl2 / アポトーシス / 細胞増殖 / HNF-1β / ｂｃｌ－２ / 卵巣子宮内膜症性嚢胞 / 腫瘍分化・増殖様式 / NF-κB |
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| Outline of Final Research Achievements |
In clinical samples, HNF-1β expression was positively correlated with the active form of NF-κB/p65 in clear cell carcinomas (CCA), and closely linked with a low nuclear grade and non-solid architecture. In cell lines, transfection of p65 resulted in increased HNF-1β mRNA and protein expression, in line with activation of the promoter. Suppression of HNF-1β expression increased apoptosis in cells, while treatment of cells stably overexpressing exogenous HNF-1β with doxorubicin abrogated apoptosis of the cells, along with increased ratio of bcl-2 relative to bax. Moreover, overexpression of HNF-1β led to upregulation of bcl-2 expression at the transcriptional level in TOV-21G cells. These data, therefore, suggest that association between HNF-1β and NF-κB signaling may participate in cell survival by alteration of apoptotic events, particularly in mitochondria-mediated pathways, through upregulation of bcl-2 expression in OCCCs.
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Report
(4 results)
Research Products
(3 results)
