Role of the signal transduction by c-kit receptor tyrosine kinase in the breast

c-kit受体酪氨酸激酶在乳腺信号转导中的作用

基本信息

批准号：
11670230
负责人：
TSUJIMURA Tohru
金额：
$ 2.3万
依托单位：
Hyogo College of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670230/
关键词：
breast c-kit receptor tyrosine kinase stem cell factor carcinogenesis c-kitレセプター・チロシンキナーゼ Stem cell factor

项目摘要

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 … More 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

C-KIT原始代码A受体酪氨酸激酶（试剂盒）和试剂盒的配体是干细胞因子（SCF）。人类转移性黑色素瘤细胞的试剂盒表达抑制肿瘤的生长和转移，而SCF诱导了表达Kit的黑色素瘤细胞。 SCF/试剂盒系统关于乳腺癌细胞的生长和转移，他将C-KIT基因浸入了人类Kit阴性转移性乳腺癌细胞系，MDA-MB-231，随后分析了其MDA-MB的生长和转移潜力-231和表达KIT的MDA-MB-231 LS在具有SCF的无血清培养基中培养，可行细胞的数量……在MDA-MB-231^<kit>细胞中增加了S的增加，但没有在培养中MDA-MB-231细胞。通过心内注射MDA -MB-231^<kit>和MDA-MB-231细胞裸鼠，其骨骼在细胞注射后28天进行了微观检查。细胞是由MDA-MB-231 MDA-MB-231细胞产生的。这两个肿瘤之间的生物学效应是不同的