2010 Fiscal Year Final Research Report
Investigation of molecular mechanism involved in the aggressiveness of micropapillary component of adenocarcinoma of lung
| Project/Area Number |
21790369
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Human pathology
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| Research Institution | Kanazawa Medical University |
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Principal Investigator |
SHIMASAKI Miyako Kanazawa Medical University, 医学部, 助教 (00440511)
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| Project Period (FY) |
2009 – 2010
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| Keywords | 肺癌 / 微小乳頭状成分 / AQP1 / 細胞移動能 / 浸潤能 |
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| Research Abstract |
Micropapillary component (MPC) has recently been accepted as a new prognostic factor of adenocarcinoma of the lung. Its molecular mechanism is, however, hardly elucidated. To establish a novel remedy for controlling advanced adenocarcinoma of the lung, molecular mechanism of the aggressiveness of micropapillary component was addressed in the present study. Cluster analyses of the gene expressions detected by cDNA microarray (Gene Chip, Affimetrix) separated adenocarcinomas with MPC from ordinary papillary adenocarcinomas. The adenocarcinomas with MPC were further divided into distinct two gene-expression patterns according to the tumor progression. While 30 genes showed significant different expressions between them, the upregulation of S100PA4 and down regulation of CXCL14 were demonstrated to be correlated with progression of MPC both at mRNA and protein levels. The present study also demonstrated the involvement of over-expression of aquaporin (AQP) 1 and 5 in the aggressive growth of adenocaricnoma with MPC, proposing the over-expression of AQP1 as an novel unfavorable prognostic factor of adenocarcinoma with MPC. In vitro studies using the transfection of AQP1 and siRNA of AQP1 gene showed increased cell motility and invasiveness of tumor cells through enhanced pseudopodia-formation. These results suggest that AQP1 and 5 may be a promising candidate molecules for gene-targeting therapy against adenocarcinoma of the lung.
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