2011 Fiscal Year Final Research Report
Mechanisms underlying regulation of Wnt signaling pathway against cancer stem-and glioma cells
| Project/Area Number |
22791348
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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 |
Cerebral neurosurgery
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| Research Institution | The University of Tokushima |
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Principal Investigator |
MIZOBUCHI Yoshifumi 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (80547993)
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| Project Period (FY) |
2010 – 2011
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| Keywords | 脳腫瘍 / REIC-Dkk3 / Wntシグナル |
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| Research Abstract |
Reduced expression in immortalized cells/ Dikkofp-3(REIC/ DKK3, REIC), a tumor suppressor gene, has been investigated in gene therapy studies in various cancers. Elsewhere we first demonstrated that REIC was down-regulated in glioblastoma(GBM) cells, and that its over-expression with plasmid vector drastically inhibited their growth via activation of intrinsic apoptotic pathway. However, whether adenovirus-mediated overexpression of REIC(Ad-REIC) contributes to anti-tumor effect in glioma remain unclear. We performed this study to assess the applicability of Ad-REIC in GBM and to verify the molecular mechanisms underlying anti-tumor effect of Ad-REIC We first document that Ad-REIC effectively inhibited the growth of GBM in a time-and dose dependent manner and induced apoptosis. We also found that Ad-REIC reduced expression of Wnt proteins and its receptor LRP6 but not ROR2 Our data suggest that interfering the activation of both canonical-and non-canonical Wnt signaling pathway via overexpression of REIC contributes at least partly to suppress cell survival in GBM.
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