2016 Fiscal Year Final Research Report
Development of artificial transcription factors for the treatment of lung and esophageal squamous cell carcinoma
| Project/Area Number |
26462141
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Respiratory surgery
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | 肺扁平上皮癌 |
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| Outline of Final Research Achievements |
Sox2 was identified as a lineage specific oncogene, recurrently amplified in lung and esophageal squamous cell carcinoma (SCC). In this study, we have developed a zinc finger based artificial transcription factor (ATF) to suppress Sox2 expression in cancer cells and termed the system ATF/Sox2. A transient transfection reporter assay demonstrated that ATF/Sox2 repressed Sox2 transcriptional activity in Sox2 expressing lung and esophageal SCC cells. A recombinant adenoviral vector: Ad-ATF/Sox2 that expresses ATF/Sox2 suppressed Sox2 at the mRNA and protein levels in lung and esophageal SCC cells. Importantly, in these cells, Ad-ATF/Sox2 decreased cell proliferation and colony formation. Moreover, Ad-ATF/SOX2 significantly inhibited tumor growth in a lung SCC xenograft mouse model. These results indicate that Sox2 silencing by ATF/ Sox2 could lead to the development of effective molecular-targeted therapies for lung and esophageal SCC.
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| Free Research Field |
医歯薬学、外科系臨床医学、呼吸器外科学
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