title: Undifferentiated embryonic cell transcription factor-1 (UTF1) inhibits the growth of cervical cancer cells by transactivating p27Kip1.
abstract: Undifferentiated embryonic cell transcription factor-1 (UTF1) is an important transcription factor during development, which plays critical roles in cell fate determination. However, its expression and function in somatic tissues remain unclear. Here, we investigated the expression pattern of the UTF1 in the human normal and cancerous lesions of cervix and found that UTF1 was downregulated in cervical carcinogenesis, which was related to the hypermethylation of UTF1 promoter. Exogenous expression of UTF1 resulted in the significant inhibition of cell proliferation in vitro and tumorigenesis in vivo through attenuating cell cycle arrest via increasing the level of p27 (Kip1) . Luciferase reporter assay indicated that the region containing an intact activating transcription factor site between nucleotides -517 and -388 of the p27 (Kip1) promoter was indispensable for its activation by UTF1. Chromatin immunoprecipitation analysis confirmed the physical interaction between UTF1 and the p27 (Kip1) promoter. Taken together, our findings reveal that UTF1 attenuates cell proliferation and is inactivated in cervical carcinogenesis through epigenetic modification, which strongly supports that UTF1 is a potential tumor suppressor.
authors.affiliation: Department of Reproductive Medicine, First Affiliated Hospital, Xi'an Jiaotong University of Medical College, Xi'an, Shaanxi 710061, China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Wu
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Zheng
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002584:Cervix Uteri / Q000378:metabolism / Q000473:pathology; D047369:Chromatin Immunoprecipitation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C436291:CDKN1B protein, human; D009687:Nuclear Proteins; D015534:Trans-Activators; C484738:UTF1 protein, human; D050760:Cyclin-Dependent Kinase Inhibitor p27; D008156:Luciferases