Wnt信号途径在不同性质乳腺组织和细胞中的表达与分布

The distribution and expression of Wnt signaling pathway in different breast tissues and cells

目的探讨乳腺癌发生发展中Wnt信号途径的改变及其关机制。方法用基因芯片和荧光实时定量聚合酶链反应（PCR）技术检测5例乳腺癌患者不同性质乳腺组织和细胞中Wnt信号途径相关基因的表达。结果与正常乳腺组织比较，癌组织中Frizzled3、Lrp5、Lrp6、Wnt9a、Wnt10a表达分别上调了8．11、10．28、9．37、15．47、19．63倍（发生频率均〉160％），DDK1、DDK4、WIF1表达分别下调了10．87、9．62、12．05倍（发生频率均≥60％）；其中Wntga、Wnt10a以及DDK1、DDK4、WIF1表达的改变主要在癌源性成纤维细胞，分别上调40．88、61．59倍和下调38．46、19．61、29．41倍（P〈0．01）；Frizzled3、Lrp5、Lrp6表达改变主要在乳腺癌干细胞，分别上调了27．36、31．41、21．25倍（P〈0．01）。结论在乳腺癌发生发展过程中，成纤维细胞源性因子Wnt9a、Wnt10a和DDK1、DDK4、WIF1的改变参与了Wnt信号途径的异常，并主要影响乳腺癌干细胞的自我更新调控。

Objective To explore the changes of Wnt signaling pathway in the breast cancer carcinogenesis and development,as well as related regulatory mechanism. Methods The gene expression of Writ signaling pathway was detected in different breast tissues and diverse ceils by gene chip technology and real-time fluorescent quantitative PCR in 5 cases of breast cancer. Results Compared with normal breast tissue,the expression levels of Frizzled 3, LrpS, Lrp6, Wnt9a,Wntl0a in the breast cancer tissue were significantly increased by 8.11-fold, 10.28-fold ,9.37-fold, 15.47-fold, 19.63-fold, respectively （ frequency,60% ） ,and those of DDK1 ,DDK4,WIF1 significantly reduced by 10.87-fold,9.62-fold, 12.05- fold, respectively （frequency ≥60% ）. The expression of Wnt9a, and Wnt10a was increased by 40.88-fold and 61.59-fold, and that of DDK1, DDK4, and WIF1 reduced by 38.46-fold, 19.61-fold,29.41-fold （P 〈 0.01 ）, respectively, mainly found in carcinoma-derived fibroblast cells. The expression of Frizzled 3, LrpS, and Lrp6 was increased by 27.36-fold, 31.41-fold, 21.25-fold, respectively （ P 〈 0.01 ）, mainly found in breast cancer stem ceils. Conclusion In the process of breast cancer carcinogenesis and development, the changes in Wnt9a, Wnt10a and DDK1, DDK4, WIF1 are involved in the anomaly about Writ signaling pathway, and mainly impact on the self-renewal regulation of breast cancer stem cells.