title: C-terminus-deleted FoxM1 is expressed in cancer cell lines and induces chromosome instability.
abstract: Forkhead Box M1 (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. In this study, we report the identification and characterization of a new variant of FoxM1, which was first isolated from our laboratory in hepatoma cell lines. Compared with wild-type FoxM1, the new variant lacks of C-terminus of FoxM1 (FoxM1ΔC), which is a transactivation domain. Reverse transcription-polymerase chain reaction and western blot analysis demonstrated that FoxM1ΔC was highly expressed in a variety of cancer cell lines such as HepG2, HeLa, A549, MB231, EJ, U2OS, Hep3B 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 to G1 progression of cell cycle, decreased Aurora B(T232) phosphorylation and increased chromosome centromere interspace. Finally, FoxM1ΔC induced instability of chromosome and formation of aneuploid cells within 1 month when expressed in HDF. In conclusion, FoxM1ΔC is expressed in cancer cells and dysregulates normal cell cycle and induces chromosome instability.
authors.affiliation: Department of Biochemistry and Molecular Biology, Brain Korea 21 Division of Cell Transformation and Restoration, Ajou University, School of Medicine, Suwon, Korea.
authors.forename: Young Hwa
authors.initials: YH
authors.lastname: Kim
authors.forename: Myoung Ho
authors.initials: MH
authors.lastname: Choi
authors.forename: Jang-Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: In Kyoung
authors.initials: IK
authors.lastname: Lim
authors.forename: Tae Jun
authors.initials: TJ
authors.lastname: Park
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D043171:Chromosomal Instability; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors