Abstract
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. Results: 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.
Highlights
DNA replication and mitosis of eukaryotic cells followed by the cell cycle of G1→S→G2→M, and cell proliferation (Qie, 2016)
This study aims to explore Cyclin D1, cyclindependent kinase 4 (CDK4) and difference of cell cycle adjusted by mitogen-activated protein kinase (MAPK) signal transduction pathway in silica and B(a)P-induced malignant transformation of human embryonic lung fibroblasts
Cyclin D1 and CDK4 phosphorylation levels in malignant transformation Human embryonic lung fibroblast (HELF) induced by silica and B(a)P were shown in Figure 1 and Table 1
Summary
DNA replication and mitosis of eukaryotic cells followed by the cell cycle of G1→S→G2→M, and cell proliferation (Qie, 2016). Cell cycle is controlled by cyclins, CDKS and CDKI periodic accumulation and degradation (Du, 2006). Cyclin D1 and CDK4 are important enzymes regulating cell from G1 to S phase transformation (Chen et al, 2017). The international agency for research on cancer (IARC), headquartered in Lyon, France, divided chemical substances into 4 levels based on human carcinogenic information and experimental animal carcinogenic data (Han et al, 2014): sufficient evidence of carcinogenicity, limited evidence of carcinogenicity (Class IA carcinogen), insufficient evidence of carcinogenicity (Class IB carcinogen), lacked evidence of carcinogenicity (Class II carcinogen). Silica was listed as a human carcinogen by IARC in 1997. B(a)P was a former carcinogen that required metabolic activation to form the final activated substance, which has been listed as a human carcinogen by IARC (Park et al, 2015; Cui et al, 2017). The carcinogenic mechanisms of silica and B(a)P are unclear
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