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

Authors
Kim, YH; Choi, MH; Kim, JH; Lim, IK; Park, TJ
Citation
Carcinogenesis, 34(8):1907-1917, 2013
Journal Title
Carcinogenesis
ISSN
0143-33341460-2180
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.
MeSH terms
Cell Cycle/geneticsCell Line, Tumor*Chromosomal InstabilityForkhead Transcription Factors/*biosynthesis/*genetics/metabolismGene Expression Regulation, NeoplasticHeLa CellsHep G2 CellsHumansMCF-7 CellsPromoter Regions, GeneticTranscription, GeneticTranscriptional Activation
DOI
10.1093/carcin/bgt134
PMID
23615399
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pathology
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
김, 장희임, 인경박, 태준
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