血行转移是乳腺癌转移的主要途径，也是患者的首要死因。循环肿瘤细胞（CTC）是转移的根源。我们研究发现乳腺癌CTC数目与肿瘤分期正相关。HER2高表达与乳腺癌远处转移密切相关，但目前机制不明。最近发现，HER-2阳性乳腺癌的PP2A活性低，PP2A可下调αⅡbβ3活性，而Src是PP2A磷酸化的关键酶，PP2A对细胞增殖凋亡有重要作用。我们推测HER2/Src/PP2A通路可能参与调控乳腺癌细胞增殖、凋亡和粘附等生物学行为。本项目将用我们已建立的膜滤过联合激光扫描仪技术检测乳腺癌患者CTC的HER2/Src/PP2A通路相关分子的表达，分析其与临床病理因素的关系；通过体外和体内研究观察干预该通路对乳腺癌细胞增殖、凋亡和粘附能力的影响，及其对荷瘤鼠转移瘤形成的影响；探讨HER2/Src/PP2A通路对乳腺癌CTC生存和转移能力的影响及其机制，为乳腺癌转移的靶向干预治疗提供新途径。

Hematogenous metastasis is the major route of metastasis in breast cancer and also the leading cause for patient death. Circulating tumor cell (CTC) is the source of the transfer. By research, we found that the CTC number was positively correlated with tumor stage in breast cancer patient. HER2 over expression is closely related to distant metastasis of breast cancer, but its mechanism is unknown. It was recently discovered that the activity of PP2A was low in HER2 positive breast cancer, and that PP2A could down-regulate the expression of αⅡbβ3. Src is a key enzyme of PP2A phosphorylation, and PP2A plays an important role in cell proliferation and apoptosis. Hence, we speculate that HER2/Src/PP2A pathway may be involved in the regulation of the biological behavior on breast cancer cell proliferation, apoptosis, and adhesion. In this project, the method of cell filtration (isolated by size of epithelial tumor cells, ISET) combined with laser scanning cytometry (LSC), which was established by us, will be used to detect the expressions of molecules related to HER2/Src/PP2A pathway of CTC in breast cancer patient, and the relationship between their expressions and the patient's clinicopathologic features will be analyzed upon. By in vitro and in vivo studies, the effects of HER2/Src/PP2A pathway intervention will be studied on breast cancer cell proliferation, apoptosis and adhesion, and on metastatic tumor formation in tumor-bearing mice. Through this project, the effects of HER2/Src/PP2A pathway on the survival and metastasic abilities of CTC will be explored in breast cancer patient, which may provide a new avenue for the targeted therapy of breast cancer metastasis.