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Overexpression of CDC25B Overrides Radiation-induced G₂-M Arrest and Results in Increased Apoptosis in Esophageal Cancer Cells¹

Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, Osaka 565-0871 Japan [H. M., Y. D., H. Y., K. K., H. T, Y. F., T. Y., M. Y., M. I., H. S., M. M.], and Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, New York 10032 [I. B. W.]

CDC25B phosphatase plays a key role in controlling G₂-M progression by dephosphorylating two inhibitory residues of CDC2 and also has been suggested to have an oncogenic property. In this study, we investigated the effect of CDC25B overexpression on radiation-induced G₂-M arrest and radiation sensitivity in esophageal cancer cells. TE8-CDC25B, in which CDC25B was overexpressed under an inducible system, was more radiosensitive than the vector control (TE8-neo) in a clonogenic survival assay. Without radiation, CDC25B overexpression had little effect on cell cycle fractions or growth rate. After 10-Gy radiation, TE8-CDC25B showed decreased G₂-M arrest and increased apoptosis, whereas TE8-neo displayed prolonged G₂-M arrest and less apoptosis. During this period, there were no differences in the protein amounts of CDC2 and cyclin B1 between the two cell lines. However, more CDC25B expression, which was reduced immediately by radiation, was sustained in TE8-CDC25B than in TE8-neo. Moreover, induction of tyrosine phosphorylation of CDC2 and reduction of CDC2 kinase activity after irradiation was less significant in TE8-CDC25B than in TE8-neo. These results indicate that cancer cells that overexpress CDC25B override G₂-M arrest by retaining CDC2 kinase activity and undergo apoptosis after radiation. This may point to an effective approach toward improving radiotherapy outcomes of various cancers.

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