| Project/Area Number |
17591681
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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 |
Urology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
FUKUMORI Tomoharu The University of Tokushima, Institute of Health Biosciences, Lecturer, 大学院ヘルスバイオサイエンス研究部, 講師 (10314874)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAYAMA Hiro-omi The University of Tokushima, Institute of Health Biosciences, Professor, 大学院ヘルスバイオサイエンス研究部, 教授 (10214446)
NISHITANI Masaaki The University of Tokushima, Institute of Health Biosciences, Associate Professor, 大学院ヘルスバイオサイエンス研究部, 助教授 (40304521)
TAKAHASHI Masayuki The University of Tokushima, Medical and Dental Hospital, Lecture, 医学部・歯学部附属病院, 講師 (50325255)
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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 |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | urogenital cancer / apoptosis / galectin / metastasis / 血管新生 |
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| Research Abstract |
Galectin-3, a member of the β-galactoside binding protein family found in the intracellular and extracellular milieu, has overexpressed in a variety of cancer cells and has been shown to be correlated with tumor progression and metastasis through the regulation of tumor proliferation, angiogenesis, and apoptosis.
Concerning the prostate cancer, after treatment with 25 μM CDDP for 48 hours, 66.3% of control LNCap cells which are garectiin-3 negative prostate cancer cell line showed DNA fragmentation, whereas only 2.9% of galectin-3 expressing LNCap cells were apoptotic. In the exposure with 300 μM etoposide for 48 hours, 48.3% of control LNCap cells were apoptotic, whereas only 15.4% of galectin-3 expressing LNCap were apoptotic. Intracellular galectin-3 inhibited mitochondrial damage after translocation from nuclei to cytoplasm, resulting inhibition of cytochrome c release and caspase-3 activation. Galectin-3 inhibited anticancer drug-induced apoptosis in the result of regulation of mitochondrial integrity, cytochrome c release, and caspase-3 activation.
Recent our microarray studies have revealed garectin-3 overexpresses in human renal cell carcinoma (RCC). The expression level of galectin-3 in RCC obtained from nephrectomy was significantly higher than that in renal parenchyma obtained from same samples. After treatment with supernatant of garectin-3 expressing cells for 12 hours, approximately 45% of CD8+ T-cells were apoptotic, whereas in galectin-3 reduced cells by siRNA, only 15-18% of the cells were apoptotic. These result indicates that galectin-3 is highly expressed in RCC and extracellular garectin-3 induces apoptosis of CD8+ T-cells.
These results suggest that galectin-3 regulated anticancer drug-induced apoptosis in prostate cancer and anti-cancer immune suppression in RCC. Taken together, it is suggested that galectin-3 is one of the target proteins for cancer chemotherapy in prostate cancer and immune escape of RCC.
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