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C-terminus deleted FoxM1 is expressed in cancer cell lines and induces chromosome instability

Kim, Young Hwa; Choi, Myoung Ho; Lim, In Kyoung; Kim, Jang-Hee; Park, Tae Jun
Department of Biochemistry & Molecular Biology
FoxM1 protein is a transcription factor and regulates cell cycle. It is commonly upregulated in human cancer tissue, and correlated with poor prognosis, suggesting that the overexpression of FoxM1 plays a critical role in carcinogenesis. Herein, we cloned a cDNA encoding a variant of FoxM1 which was isolated from hepatoma cell lines. Compared with wild type FoxM1, the variant lacks of C-terminus of FoxM1 (FoxM1∆) which is a transactivation domain. RT-PCR and Western blot analysis demonstrated that FoxM1∆ were highly expressed in a variety of cancer cell lines such as HepG2, HeLa, A549, and MCF7, but not expressed in normal human dermal fibroblast (HDF). Immunoprecipitation assay revealed that FoxM1∆ interacted with wild type FoxM1. Furthermore, FoxM1∆ bound to FoxM1 targeted gene promoter region and correlated with dysregulation of wild type FoxM1. FoxM1∆ delayed G2/M phase of cell cycle, decreased Aurora BT232 phosphorylation, and increased chromosome centromere interspace. Finally, FoxM1∆ induced instability of chromosome and formation of aneuploid cells within a 1 month when expressed in human dermal fibroblast (HDF). In conclusion, FoxM1∆ is expressed in cancer cells, and dysregulates normal cell cycle and induces chromosome instability.
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