抑癌基因Syk(L)在乳腺癌中具有转录抑制因子功能

Tumor suppression gene Syk(L) is a transcriptional repressor in breast cancer

目的:研究移位到细胞核内抑癌基因Syk(L)在乳腺癌中的生物学功能,探讨Syk(L)抑制乳腺癌发展的可能机制。方法:将Syk(L)、失去激酶活性的Syk(L)以及Syk(L)各个功能域按正确读框插入到含有Gal4基因DNA结合功能域(Gal4-DBD)的pFA载体中,并在HEK293细胞中表达;利用Gal4荧光素酶报告基因的方法检测在乳腺癌细胞中Syk(L)、失去激酶活性的Syk(L)以及Syk(L)各个功能域对基因转录的影响。结果:在乳腺癌细胞MB231和MB435中,与Gal4-DBD结合的Syk(L)可以下调启动子上含有Gal4结合位点的萤光素酶基因的表达,这种调节与Syk(L)的激酶活性无关,是通过Syk(L)的SH2功能域和KD功能域完成的。结论:在乳腺癌中,Syk(L)具有转录抑制功能,该功能与Syk(L)的激酶活性无关,是通过Syk(L)的SH2功能域和激酶功能域实现的。Syk(L)在乳腺癌中的抑癌作用可能与其转录抑制功能有关。

AIM： To study the Syk（L） biological function in breast cancer and to explore the possible mechanism of tumor suppression gene Syk（L）. METHODS： Syk（L） ,kinase inefficient Syk（L） or the domains of Syk（L） were fused with the DNA binding domains of Gal4 to make recombinant plasmids, which were cotransfected with pFR and pCMV - β - gal into human breast cancer cells MB231 and MB435. Gal4 luciferase reporter assay was used to observe the transcriptional regulation function of Syk （L）. RESULTS ： Syk （ L）, fused with DNA binding domain of Gal4, was capable of down -regulating the expression of luciferase whose promoter contains 5 Gal4 binding sites in human breast cancer cells, MB231 and MB435. This kind of down- regulation was unrelated to Syk（ L）＇s kinase activity,and was decided by the SH2 domain and kinase domain of Syk （L）. CONCLUSION： Syk （L） possesses transcriptional repressor function in breast cancer,which is unrelated to Syk（L） ＇s kinase activity. Both the SH2 domain and kinase domain of Syk（L） have the transcriptional repressor function. The tumor suppression role of Syk（L） is maybe associated with its transcriptional repression function in breast cancer.