Analysis of Signal Transduction Pathway of Syk in Breast Cancer Cells-as a comparison with that of Her2

乳腺癌是女性最常见的癌症之一。蛋白酪氨酸激酶已被证明参与乳腺癌的发病机制。Her 2是一种蛋白酪氨酸激酶，被认为具有致癌功能，而Syk是另一种蛋白酪氨酸激酶，显示出抑瘤潜力。我们试图比较这两种激酶的表达及其下游信号系统。我们估计这些激酶的表达使用免疫印迹在人乳腺癌细胞系。在这些细胞系中的一些中，一种乳腺癌细胞系MDAMB 453表达Her 2但不表达Syk。当Syk被引入MDAMB 453中时，Her 2的表达根据Syk的表达水平而下降。与模拟细胞相比，Syk导入的MDAMB 453克隆的生长速率降低。在MDAMB 453克隆中，阿霉素诱导Syk表达增加，这与聚ADP-核糖聚合酶（半胱天冬酶的底物）的降解相关。这些数据暗示了这些激酶在乳腺癌发生中的相反功能的机制，其中Syk在暴露于癌症治疗剂时增强细胞凋亡。

Breast cancer is one of the most popular cancers in women. Protein-tyrosine kinases have been shown to be involved in the pathogenesis of breast cancer. Her2 is a protein-tyrosine kinase which is believed to have oncogenic function, whereas Syk is another protein-tyrosine kinase which displays oncostatic potential. We have attempted to compare these two kinases focusing on their expression and their down stream signaling system. We estimated the expression of these kinases using immunoblotting in human breast cancer cell lines. In some of these cell lines, one breast cancer cell line, MDAMB453 expressed Her2 but no Syk. When Syk is introduced in MDAMB453, the expression of Her2 declined according to the expression level of Syk. The growth rate of Syk-introduced MDAMB453 clones was decreased as compared to that of mock cells. In MDAMB453 clones, administration of adriamycin induced an increase in Syk expression, which was correlated with a degradation of polyADP-ribose polymerase, a substrate of caspases. These data imply a mechanism of the opposite functions of these kinases in breast cancer carcionogenesis, in which Syk enhances apoptosis upon an exposure to cancer therapeutics.