TGF-β1和TGF-α在膀胱癌侵袭和转移中的作用

Effects of transforming growth factor-β_1 and transforming growth factor-α on the growth and invasive potentials of human bladder tumor cells

目的 探讨转化生长因子 β1(TGF β1)和转化生长因子 α(TGF α)对膀胱癌细胞株 (EJ)生长的影响以及促进膀胱癌侵袭和转移的可能途径。 方法 采用MTT、WesternBlot和RT PCR方法 ,观察TGF β1和TGF α对EJ细胞株生长以及在mRNA和蛋白水平上对金属基质蛋白酶(MMPs)和组织特异性金属蛋白酶抑制剂 2 (TIMP 2 )表达的影响。 结果 (1)TGF β1和TGF α对EJ细胞生长存在抑制趋势 ,但差别无显著性意义。 (2 )TGF β1和TGF α作用于EJ细胞 48h时 ,MMP 2、TIMP 2、MT1 MMPmRNA表达降低 ;TGF β1组MMP 9mRNA表达增加 ,而对照组和TGF α组无MMP 9mRNA表达。 (3)当TGF β1浓度为 0 .1、1.0ng/ml时 ,增加细胞培养上清液中MMP 2蛋白含量对TIMP 2蛋白水平无影响。当浓度为 5 .0、10 .0ng/ml时对MMP 2无影响而降低TIMP 2表达 ;TGF α在浓度为 1.0、5 .0、10 .0ng/ml时 ,对MMP 2蛋白表达无影响而降低TIMP 2表达 ;在 10 0 .0ng/ml时增加MMP 2蛋白表达而对TIMP 2表达无影响 ;无论在对照组和实验组均未检测到MMP 9。 结论 TGF β1、TGF α不能抑制EJ细胞生长 ,参与肿瘤侵袭和转移作用可能与调节MMPs、TIMP

Objective To study the effects of transforming growth factor β1 (TGF β1) and transforming growth factor α (TGF α) on the growth and invasive potentials in human bladder tumor cells. Methods The effects of TGF β1 and TGF α on the growth of EJ cell line and the effects on MMPs and TIMP 2 were studied by means of MTT,Western Blot and RT PCR methods. Results (1)TGF β1 and TGF α tended to inhibit the growth of EJ cells but statistically nonsigficant.(2)Higher levles of MMP 9 mRNA but lower levels of MMP 2,TIMP 2,MT1 MMP mRNA were found in EJ cells following the treatment with TGF β1.The same was true for the expression of MMP 2,TIMP 2 mRNA in TGF α groups.However,MMP 9 mRNA was not found in both TGF α groups and the control groups. (3)TGF β1 ( 0.1 , 1.0 ng/ml) enhanced MMP 2 protein but not the TIMP 2 protein,while TGF β1 ( 5.0 , 10.0 ng/ml)decreased TIMP 2 protein but not on MMP 2.In TGF α groups,when the concentration was 1.0 , 5.0 , 10.0 ng/ml,TIMP 2 protein expression was decreased but MMP 2 did not.When the concentration reached 100.0 ng/ml,it increased MMP 2 protein level,not the TIMP 2 protein. Conclusions TGF β1 and TGFα do not inhibit the proliferation of EJ cells whereas the enhanced invasiveness and metastasis may be associated with regulating the expression of MMPs and TIMP 2.