目的：分析视网膜母细胞瘤（retinoblastoma, Rb）基因和磷酸化Rb（P-Rb）在人乳腺癌组织中的表达及在乳腺癌上皮间质转化（epithelial-mesenchymal transition，EMT）中的意义。方法： 选取2009年1月至2009年8月在河北医科大学第四医院进行手术切除的65例乳腺癌患者标本，利用免疫组织化学法检测乳腺癌组织中Rb、P-Rb、上皮细胞标记物CDH1和间质细胞标记物Vimentin的表达状况，分析二者表达与乳腺癌患者临床病理学指标和预后的关系。利用real-time PCR及Western blotting方法检测在TGFβ诱导的EMT过程中Rb及P-Rb的表达变化。结果：乳腺癌组织中，Rb和P-Rb蛋白表达阳性率分别为55.38%和50.77%。P-Rb蛋白表达与乳腺癌患者的肿瘤大小、临床分期及淋巴结转移状况呈正相关。CDH1和Vimentin蛋白表达阳性率分别为76.92%和43.08%。CDH1蛋白表达与乳腺癌患者的肿瘤大小、临床分期及淋巴结转移状况呈负相关。Vimentin蛋白表达与乳腺癌患者的肿瘤大小、临床分期及淋巴结转移状况呈正相关。Rb及P-Rb蛋白表达均与CDH1蛋白表达呈正相关，与Vimentin蛋白表达呈负相关。P-Rb蛋白表达阳性的乳腺癌患者的总五年生存率明显低于P-Rb蛋白表达阴性的患者；CDH1蛋白表达阳性的乳腺癌患者的总五年生存率明显高于CDH1蛋白表达阴性的患者，Vimentin蛋白表达阳性的乳腺癌患者的总五年生存率明显低于Vimentin表达阴性的患者。在TGFβ诱导的HMLE细胞发生EMT的过程中，Rb的表达显著下降，P-Rb的表达显著上升。结论：Rb的磷酸化失活影响了乳腺癌细胞上皮间质转化的过程，与乳腺癌的转移密切相关。

Objective:To investigate the expression of retinoblastoma (Rb) and phosphate retinoblastoma (P-Rb) in human breast cancer tissues and their significance during the process of epithelial-mesenchymal transition (EMT). Methods: 65 samples from patients with breast cancer that surgically removed in the Fourth Clinical Hospital of Hebei Medical University from Jan. to Aug. 2009 were retrospectively examined in this study. Immunohistochemistry was used to examine the expression of Rb, P-Rb, CDH1 and Vimentin in the breast cancer tissues of 65 cases. The correlation between their expression and clinicopathological parameters and prognosis of the case wih breast cancer was analyzed. Real-time PCR and Western blotting were used to examine the expression change of Rb and P-Rb in TGFβ-induced EMT. Results: Expression rates of Rb and P-Rb in the breast cancer tissues were 55.38% and 50.77%, respectively. Expression of P-Rb was positively correlated with tumor size, clinical stages and lymph node metastasis. Expression rates of CDH1 and Vimentin in the breast cancer were 76.92% and 43.08% respectively. Expression of CDH1 negatively correlates with tumor size, clinical stages and lymph node metastasis, while expression of Vimentin positively correlates with tumor size, clinical stages and lymph node metastasis. Both expressions of Rb and P-Rb positively correlates with expression of CDH1, but negatively correlates with expression of Vimentin. Overall 5 years survival rate of patients with P-Rb positive breast cancer was significantly lower than that of patients with P-Rb negative breast cancer; overall 5 years survival rate of patients with CDH1 positive breast cancer was significantly higher than that of patients with CDH1 negative breast cancer; overall 5 years survival rate of patients with Vimentin positive breast cancer was significantly lower than that of patients with Vimentin negative breast cancer. Expression of Rb was down regulated and that of P-Rb up regulated in TGFβ induced EMT of HEML cells.Conclusion: Inactivation of Rb with phosphorylation affected EMT and correlated with breast cancer metastasis.

河北省科技支撑计划项目资助（No.14277732D）