| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Research Abstract |
The c-kit proto-oncogene encodes a receptor tyrosine kinase (KIT), and the ligand for KIT is stem cell factor (SCF). KIT is expressed in melanocytes and normal mammary epithelium, but KIT expression remarkably decreases in melanomas and breast cancers. It has recently been reported that the enforced KIT expression in human metastatic melanoma cells inhibits tumor growth and metastasis in nude mice, and SCF induces apoptosis in the KIT-expressing melanoma cells. These results suggest that the loss of KIT expression allows melanoma cells to escape SCF/KIT-mediated apoptosis. In an effort to determine the effects of SCF/KIT system on growth and metastasis of breast cancer cells, we transfected the murine c-kit gene into the human KIT-negative metastatic breast cancer cell line, MDA-MB-231, and subsequently analyzed its growth and metastatic potency. When MDA-MB-231 and KIT-expressing MDA-MB-231 (MDA-MB-231^<KIT>) cells were cultured in serum-free medium with SCF, the number of viable cell
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s increased in culture of MDA-MB-231^<KIT> cells, but not in culture of MDA-MB-231 cells. Moreover, [^3H]-thymidine incorporation assay showed that SCF induced the proliferation of MDA-MB-231^<KIT> cells. These results indicate that SCF/KIT-mediated signal promotes the proliferation of MDA-MB-231^<KIT> cells in vitro. Bone metastasis was produced by an intracardiac injection of MDA-MB-231^<KIT> and MDA-MB-231 cells into nude mice, and their bones were microscopically examined 28 days after the cell injection. The number of bone metastasis produced by MDA-MB-231^<KIT> cells was much more than that produced by MDA-MB-231 cells, and the area of bone metastasis produced by MDA-MB-231^<KIT> cells was larger than that produced by MDA-MB-231 cells. Since SCF is abundantly produced by bone marrow stromal cells, SCF/KIT-mediated signal seems to promote the proliferation of MDA-MB-231^<KIT> cells in vivo. Thus, although KIT expression similarly decreases in melanomas and breast cancers, it is likely that the biological effects of KIT are different between these two tumors. Less
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