| Budget Amount *help |
¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Research Abstract |
In Japan, prostate cancer (Pca) morbidity and mortality have been increasing, presumably due to changes in dietary habits, higher rates of screening and an expanding elderly population. Recent studies shown that high-fat diet (HFD) active PI3K and MAPK by the modulate many important growth factors including IGF-1, FGF and EGF in prostate cancer (Kalaany NY et al, Nature, 2009).
Recently we demonstrated HFD influence progression of prostate cancer, and found that many receptors of growth factors and cytokine implicated progression of prostate cancer in the prostate cancer xenograft (Narita S et al, Prostate, 2008)。
In this study, we investigated the role of Fn14 on prostate-cancer progression using prostate cancer cells, LNCaP prostate cancer xenograft model and human prostate cancer samples. Fn14 and its ligand TWEAK were highly expressed in the androgen independent prostate cancer cells, and Fn14 was shown to modulate expression of matrix metalloproteinase-9 (MMP-9), and influence the proliferation and invasiveness of prostate cancer cells. Clinically, high expression of Fn14 was significantly associated with higher PSA recurrence rate in patients who underwent radical prostatectomy.
In conclusion, the over expression of Fn14 may contribute to multiple malignant cellular phenotypes associated with prostate cancer progression, in part via MMP-9. TWEAK-Fn14 signaling may be a novel therapeutic target of prostate cancer.
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