A role of β-catenin signaling loop on cell proliferation and differentiation of endometrial carcinomas : Implication for gene therapy
| Project/Area Number |
17590315
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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 |
Human pathology
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| Research Institution | Kitasato University |
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Principal Investigator |
SAEGUSA Makoto Kitasato University, Pathology, Associate Professor, 医学部, 助教授 (00265711)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | endometrial carcinoma / beta-catenin / TCF4 / p300 / p16 / p53 / p14 / β-カテニン / p16^<INK4A> / pRb / 子宮内膜癌細胞 |
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| Research Abstract |
Nuclear stabilization of β-catenin and its interaction with TCF/LEF factors are key events in transduction of the Wnt/ β-catenin signal pathway. We show here that β-catenin can directly induce transcription from the TCF4 promoter, the effect being enhanced by the p300 coactivator. In clinical cases, nuclear β-catenin accumulation was found to frequently overlap with TCF4 immunoreactivity in morules and surrounding glandular carcinoma lesions, showing a significant positive correlation (r=0.82, p<0.0001), in contrast to areas of squamous metaplasia (SqM) within Em Cas. The TCF4 promoter contains a single consensus TCF binding site that is critical for activation by β-catenin. The p300 coactivator appears sufficient to enhance β-catenin-dependent transcription, again with TCF4-dependence, indicating that a positive feedback loop of TCF4 expression mediated by β-catenin/p300 may be important for initial steps during trans-differentiation of Em Ca cells. In addition, transcriptional activation of p16^<INK4A> promoter by active form β-catenin occurred in a TCF4-independent manner. Moreover, cell proliferation was accompanied with phosphorylation of pRb and increased p16^<INK4A>, expression, while its inhibition by serum starvation caused decreased expression of total pRb but not p16^<INK4A>, resulting in high relative amounts of the latter, indicating that induction of p16^<INK4A> mediated by nuclear β-catenin and p21^<WAF1>, along with loss of pRb expression, may be important for initial steps during trans-differentiation of Em Ca cells.
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Report
(3 results)
Research Products
(6 results)
