二氧化硅和苯并芘诱导人胚肺成纤维细胞恶性转化过程中MAPK和细胞周期蛋白D1/细胞周期蛋白依赖性激酶4的激活
Activation of MAPK and Cyclin D1/CDK4 in Malignant Transformation of Human Embryonic Lung Fibroblasts Induced by Silica and Benzopyrene.
作者信息
Wang Huan, Xiao Shuyu, Tang Yali, Han Ke, Zhang Zheng, Jin Yulan, Shen Fuhai
机构信息
1Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, No. 21 Bohai Road, Caofeidian District, Tangshan, Hebei Province, China.
Tangshan City Center for Disease Control and Prevention, 52 North Weiguo Road, Tangshan, Hebei Province, China.
出版信息
Asian Pac J Cancer Prev. 2020 Feb 1;21(2):295-300. doi: 10.31557/APJCP.2020.21.2.295.
OBJECTIVE
Silica and Benzo(a)pyrene are listed as carcinogens. This study aims to explore Cyclin D1, CDK4 and difference of cell cycle adjusted by MAPK signal transduction pathway in silica and B(a)P-induced malignant transformation of human embryonic lung fibroblasts.
METHODS
Activity of the subfamily (ERK, p38 and JNK) of mitogen-activated protein kinase (MAPK), cyclin D1 and CDK4 (cyclin dependent kinase) were evaluated using Human embryonic lung fibroblast (HELF) purchased from the cell room, basic research institute, Chinese Academy of Medical Sciences. The expression of cyclin D1 and CDK4 (cyclin dependent kinase) were measured in silica and B(a)P induced malignant using Western blot (WB) assay.
RESULT
P-ERK and P-JNK expression increased significantly (P<0.01), while CDK4 and P-p38 expression decreased (P<0.01, P<0.05) in silica-induced malignant transformation cells compared with the control group. P-ERK, P-JNK and Cyclin D1 expression increased (P<0.01, P<0.01, P<0.05) in B(a)P-induced group compared with the control group. P-ERK and P-JNK expression decreased (P<0.01), while P-p38, Cyclin D1 and CDK4 expression increased (P<0.05, P<0.05, P<0.01) in B(a)P-induced group compared with the silica-induced group.
CONCLUSION
MAPK and cyclin D1/CDK4 activation expressed differently in human embryo lung fibroblasts malignant transformation induced by silica and benzopyrene.
目的
二氧化硅和苯并(a)芘被列为致癌物。本研究旨在探讨细胞周期蛋白D1、细胞周期蛋白依赖性激酶4（CDK4）以及丝裂原活化蛋白激酶（MAPK）信号转导通路调节的细胞周期在二氧化硅和苯并(a)芘诱导人胚肺成纤维细胞恶性转化中的差异。
方法
使用从中国医学科学院基础医学研究所细胞室购买的人胚肺成纤维细胞（HELF）评估丝裂原活化蛋白激酶（MAPK）亚家族（细胞外调节蛋白激酶（ERK）、p38和应激活化蛋白激酶（JNK））、细胞周期蛋白D1和细胞周期蛋白依赖性激酶4（CDK4）的活性。采用蛋白质免疫印迹法（WB）检测二氧化硅和苯并(a)芘诱导恶性转化细胞中细胞周期蛋白D1和细胞周期蛋白依赖性激酶4（CDK4）的表达。
结果
与对照组相比，二氧化硅诱导的恶性转化细胞中P-ERK和P-JNK表达显著增加（P<0.01），而CDK4和P-p38表达降低（P<0.01，P<0.05）。与对照组相比，苯并(a)芘诱导组中P-ERK、P-JNK和细胞周期蛋白D1表达增加（P<0.01，P<0.01，P<0.05）。与二氧化硅诱导组相比，苯并(a)芘诱导组中P-ERK和P-JNK表达降低（P<0.01），而P-p38、细胞周期蛋白D1和CDK4表达增加（P<0.05，P<0.05，P<0.01）。
结论
MAPK和细胞周期蛋白D1/CDK4激活在二氧化硅和苯并芘诱导的人胚肺成纤维细胞恶性转化中表达不同。
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