BRK tyrosine kinase expression in a high proportion of human breast carcinomas
BRK tyrosine kinase expression in a high proportion of human breast carcinomas
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DOI：
10.1038/sj.onc.1201241
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发表时间：
1997-08-14
期刊：
影响因子：
8
通讯作者：
Crompton, MR
中科院分区：
文献类型：
--
作者：
Barker, KT;Jackson, LE;Crompton, MR
BRK是最近描述的非受体蛋白酪氨酸激酶，其mRNA被发现在人乳腺肿瘤和乳腺癌细胞系中表达，BRK在成纤维细胞和乳腺上皮细胞中的表达已被证明增强它们独立生长锚定的能力，并且表达BRK的乳腺上皮细胞获得对表皮生长因子的增强的促有丝分裂应答，为了进一步研究BRK在乳腺癌中的表达，我们分离了特异性识别该蛋白的单克隆抗体。尽管BRK表达在正常乳腺组织和良性病变中很低或检测不到，但大约三分之二的乳腺肿瘤表达了可感知的水平，27%的肿瘤过度表达BRK，这种表达模式反映在来自正常乳腺上皮细胞或来自癌的细胞系的比较中，发现BRK表达在整个细胞周期中是恒定的，并且不随细胞增殖速率而变化。考虑到这种表达数据，结合BRK被证实的解除乳腺上皮细胞增殖的能力，支持了BRK在高比例乳腺癌中的过度表达是其演变中的功能重要因素的假设。
BRK is a recently described non receptor protein tyrosine kinase whose mRNA was found to be expressed in human breast tumours and breast cancer cell lines, Expression of BRK in fibroblasts and mammary epithelial cells has been shown to enhance their ability to grow anchorage independently, and mammary epithelial cells expressing BRK acquire a potentiated mitogenic response to epidermal growth factor, In order to investigate further the expression of BRK in breast cancers, we have isolated monoclonal antibodies specifically recognising the protein, Whereas BRK expression was low or undetectable in normal mammary tissue and benign lesions, approximately two-thirds of breast tumours expressed appreciable levels, and 27% of tumours over expressed BRK by fivefold or more (up to 43x), This expression pattern was mirrored in a comparison of cell lines derived either from normal mammary epithelial cells or from carcinomas, BRK expression was found to be constant throughout the cell cycle, and did not vary with cell proliferation rate, A consideration of this expression data, in conjunction with BRK's demonstrated ability to deregulate the proliferation of mammary epithelial cells, supports the hypothesis that the over expression of BRK in a high proportion of breast carcinomas is a functionally important factor in their evolution.