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与乳腺癌的发病机制有关。HER2是一种蛋白酪氨酸激酶，被认为具有致癌功能，而Syk是另一种具有抑癌潜能的蛋白酪氨酸激酶。我们试图比较这两种蛋白的表达及其下游信号系统。我们使用免疫印迹技术估计了这些激酶在人类乳腺癌细胞系中的表达。在其中一些细胞系中，一种乳腺癌细胞系MDAMB453表达Her2，但不表达Syk。在MDAMB453中引入Syk后，Her2的表达随Syk表达水平的升高而下降。与模型细胞相比，Syk导入的MDAMB453克隆的生长速度明显降低。在MDAMB453克隆中，给予阿霉素诱导Syk表达增加，这与caspase底物多聚ADP核糖聚合酶的降解有关。这些数据暗示了这些激酶在乳腺癌发生中相反功能的机制，在这种机制中，Syk在接触癌症治疗药物时促进了细胞凋亡。

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.