Function And Mechanism Of Cyclin B1 In The Development Of Human Esophageal Squamous Cell Carcinoma

Human esophageal squamous cell carcinoma (ESCC) is one of the most common malignant cancers in the world with high occurrence and death rate. But the molecular mechanism in ESCC still remains unclear. Cancer is a kind of disease caused by progressingly unbalanced cell cycle control. Cyclin B1 is a key regulator of progression through the G2/M transition during the cell cycle. Although Cyclin B1 proteins are overexpressed in various types of human cancers, the relationship between Cyclin B1 status in cancer development and its function remains unknown.Cyclin B1 protein expression was first examined in clinical specimens of esophageal squamous cell carcinoma by immunohistochemisty. The amount of Cyclin B1 protein in ESSC was considerably higher than that in nomal adjacent tissues. Cyclin B1 overexpression was correlated with differentiation and invasion.The stable Cyclin B1 overexpression cell line was constructed by gene transfection into human esophageal cancer cell line KYSE150. The results on cell biological experiment showed that Cyclin B1 overexpression promoted the esophageal cancer cell proliferation and invasion ability in vitro. Nude mouse tumorigenesis indicated that Cyclin B1 overexpression enhanced the tumor formation ability and invasion ability to the adjacent tissues. In addition, Cyclin B1 overexpression led to the metastasis of local lymph node and lung.To further prove that Cyclin B1 played the role in the esophageal cancer development, the stable Cyclin B1 silencing cell line was established by RNA interference against Cyclin B1 into human esophageal cancer cell line EC9706. Cyclin B1 silencing could inhibit the esophageal cancer cell proliferation, invasion and metastasis ability in vitro and in vivo, remarkingly reduce the lung metastasis.The expression of genes related with cancer invasion and metastasis was detected in the Cyclin B1 gene transfectant esophageal cancer cell line. The overexpression of Cyclin B1 led to the reduction of TGF-β. This result was validated by immunofluorescence staining.Taken together, Cyclin B1 plays an important role in malignant proliferation, invasion and metastasis in esophageal squamous cell carcinoma. Cyclin B1 possibly inactivates TGF-β/Smad signal transduction pathway and promotes the development of esophageal cancer by downregulation of TGF-β. This provides a good clue to explore the mechanism that Cyclin B1 promotes the development of esophageal squamous cell carcinoma by downregulation of TGF-β.