透明质酸结合蛋白对肿瘤细胞表达cyclinE及p27^(kip1)的影响

Influences of hyaluronic acid binding protein on expressions of human cancer cells cyclin E and p27^(kip1)

目的 研究透明质酸结合蛋白 (HABP)对人乳腺癌、前列腺癌细胞和牛血管内皮细胞cyclinE及p2 7kip1 表达的影响。方法 将人脑透明质酸结合蛋白 (hbHABP)全长cDNA转染到人乳腺癌细胞 (MDA43 5 )和前列腺癌细胞 (TSU)中 ,研究细胞周期蛋白cyclinE及细胞周期蛋白依赖性激酶抑制物 p2 7kip1 表达的变化。再将这些转基因细胞的培养上清液 (CM )加入牛主动脉血管内皮细胞 (ABAE)的培养上清液中 ,观察CM对ABAE的 p2 7kip1 表达的影响。结果 MDA43 5和TSU细胞转染hbHABP基因后 ,cyclinE的表达水平均明显低于对照组细胞 ,而 p2 7kip1的表达水平均升高。ABAE细胞受CM作用后 ,p2 7kip1的表达水平也高于对照组细胞。结论 hbHABP可能具有下调肿瘤细胞周期蛋白cyclinE和上调细胞周期蛋白依赖性激酶抑制物 p2 7kip1 的作用 ,从而抑制肿瘤细胞的生长 ;同时 ,hbHABP促进血管内皮细胞 p2 7kip1 的表达 ,可以抑制肿瘤新生血管的形成。

Objective To study the influences of hyaluronic acid binding protein (HABP) on expressions of human cancer cells cyclin E and p27 kip1 and adult bovine arterial endothelial cells (ABAE) p27 kip1 . Methods Full length cDNA of human brain hyaluronic acid binding protein (hbHABP) was transfected into human breast cancer cell line(MDA435) and prostatic cancer cell line (TSU). Cyclin E and p27 kip1 expression from these transfectants were detected by Western blot. In addition, conditioned medium (CM)from these transfectants was added to the cultured ABAE, and the p27 kip1 expression was also determined. Results Cyclin E expression level was much decreased in both MDA435 and TSU cells, whereas p27 kip1 expression level was greatly increased. There was also an increasing expression of p27 kip1 in ABAE cells affected by CM. Conclusion hbHABP may have inhibiting effects on human breast cancer and prostate cancer cells growth through the following mechanisms, inhibiting cancer cells cyclin E expression and inducing inhibitor of cyclin dependent kinase p27 kip1 expression, inhibiting tumor angiogenesis by increasing endothelial cells p27 kip1 expression.