title: Stat3 induces oncogenic Skp2 expression in human cervical carcinoma cells.
abstract: Dysregulated Skp2 function promotes cell proliferation, which is consistent with observations of Skp2 over-expression in many types of human cancers, including cervical carcinoma (CC). However, the molecular mechanisms underlying elevated Skp2 expression have not been fully explored. Interleukin-6 (IL-6) induced Stat3 activation is viewed as crucial for multiple tumor growth and metastasis. Here, we demonstrate that Skp2 is a direct transcriptional target of Stat3 in the human cervical carcinoma cells. Our data show that IL-6 administration or transfection of a constitutively activated Stat3 in HeLa cells activates Skp2 mRNA transcription. Using luciferase reporter and ChIP assays, we show that Stat3 binds to the promoter region of Skp2 and promotes its activity through recruiting P300. As a result of the increase of Skp2 expression, endogenous p27 protein levels are markedly decreased. Thus, our results suggest a previously unknown Stat3-Skp2 molecular network controlling cervical carcinoma development.
authors.affiliation: Shanghai Medical College of Fudan University, Shanghai 200032, China.
authors.forename: Hanhui
authors.initials: H
authors.lastname: Huang
authors.forename: Wenrong
authors.initials: W
authors.lastname: Zhao
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
mesh_terms: D002277:Carcinoma / Q000235:genetics*; D045744:Cell Line, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics; D009857:Oncogenes; D011401:Promoter Regions, Genetic; D055550:Protein Stability; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000235:genetics*; D050880:p300-CBP Transcription Factors / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D044786:S-Phase Kinase-Associated Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050760:Cyclin-Dependent Kinase Inhibitor p27; D008156:Luciferases; D050880:p300-CBP Transcription Factors