C-terminus deleted FoxM1 is expressed in cancer cell lines and induces chromosome instability
Kim, Younghwa; Choi, Myoung Ho; Lim, In Kyoung; Park, Tae Jun
Department of Biochemistry & Molecular Biology, Ajou University School of Medicine
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 (FoxM1ΔC) which is a transactivation domain. RT-PCR and Western blot analysis demonstrated that FoxM1ΔC 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 FoxM1ΔC interacted with wild type FoxM1. Furthermore, FoxM1ΔC bound to FoxM1 targeted gene promoter region and correlated with dysregulation of wild type FoxM1. FoxM1ΔC delayed G2/M phase of cell cycle, decreased Aurora BT232 phosphorylation, and increased chromosome centromere interspace. Finally, FoxM1ΔC induced instability of chromosome and formation of aneuploid cells within a 1 month when expressed in human dermal fibroblast (HDF). In conclusion, FoxM1ΔC is expressed in cancer cells, and dysregulates normal cell cycle and induces chromosome instability.
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