2005 Fiscal Year Final Research Report Summary
Growth inhibition of non-small cell lung cancer cells by AP-1 blockade using a cJun dominant negative mutant, TAM67
| Project/Area Number |
16590729
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
KINOSHITA Ichiro Hokkaido Univ., Grad.School of Med., Lecturer, 大学院・医学研究科, 講師 (40343008)
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| Project Period (FY) |
2004 – 2005
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| Keywords | lung cancer / gene therapy / AP-1 / molecular biology / transcription factor / transformation / c-jun |
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| Research Abstract |
AP-1, a transcription factor transducing multiple mitogen growth signals, may be a useful target for gene and molecular target therapy. A previous study has demonstrated that cJun, a major constituent of AP-1, is frequently overexpressed in non-small cell lung cancers (NSCLCs). Therefore, in this study, we investigated the effect of AP-1 blockade on the growth of NSCLC cells using a cJun dominant negative mutant, TAM67. Transiently transfected TAM67 inhibited AP-1 transcriptional activity in NSCLC cell lines, H520 and H1299 cells. Colony forming efficiency of H1299 was much reduced by TAM67, while that of H520 was not. To elucidate the effect of TAM67 on the growth of H1299, we established H1299 clones that expressed TAM67 under the control of doxycycline-inducible promoter. Luciferase assay confirmed that the induction of TAM67 decreased AP-1 activity. MTT assay demonstrated that TAM67 inhibited cell growth. Flow cytometry analysis showed that TAM67 induced G1 cell cycle arrest. TAM67 also inhibited anchorage-independent growth determined by soft agarose assay, and Furthermore, we demonstrated that tumor growth was inhibited under the condition of expressing TAM67 in nude mice. These results suggest that AP-1 transcriptional activity plays an essential role in the growth of at least a part of NSCLC cells and that AP-1 can be a potential target for the treatment of NSCLCs.
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