title: MZF-1/Elk-1 Complex Binds to Protein Kinase Cα Promoter and Is Involved in Hepatocellular Carcinoma.
abstract: In this study, the molecular mechanism of protein kinase C alpha (PKCα) gene regulation in hepatocellular carcinoma (HCC) involving Ets-like protein-1 (Elk-1) and myeloid zinc finger-1 (MZF-1) was investigated. The luciferase reporter assay results revealed that the presence of both MZF-1 and Elk-1 significantly contributed to the upregulation of PKCα gene transcription activity, and the transcriptional activity decreased when the transfection included a DNA-binding-deficient (∆DBD) gene vector of either MZF-1 or Elk-1 DNA-binding deficiency (MZF-1∆DBD or Elk-1∆DBD), thereby indicating that the enhanced expression of PKCα was caused by the binding of MZF-1 and/or Elk-1 with the PKCα promoter. We investigated MZF-1 and Elk-1 to determine whether they bind to each other. The results of immunoprecipitation (IP), Co-IP, chromatin IP (ChIP), and Re-ChIP analyses indicated that Elk-1 can directly bind to the N-terminal region of MZF-1 and MZF-1 can directly bind to the C-terminal region of Elk-1 to form a complex before attaching to the PKCα promoter. Furthermore, when MZF-1∆DBD or Elk-1∆DBD was added to the cells, PKCα expression decreased, and cell proliferation, migration, invasion, and tumorigenicity also decreased. These findings suggest that PKCα expression in HCC could be stimulated by the formation of MZF-1/Elk-1 complex, which directly binds to the PKCα promoter.
authors.affiliation: Department of Life Science, National Chung Hsing University, Taichung, Taiwan; Department of Surgery, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan.
authors.forename: Chia-Herng
authors.initials: CH
authors.lastname: Yue
authors.affiliation: Graduate Institute of Chinese Medical Science, School of Chinese Medicine, China Medical University, Taichung, Taiwan; Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Basic Medical Science Education Center, College of Medicine and Health, Fooyin University, Kaohsiung, Taiwan.
authors.forename: Jen-Hsiang
authors.initials: JH
authors.lastname: Tsai
authors.affiliation: Department of Surgery, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan; Department of applied Chemistry, National Chiayi University, Chiayi, Taiwan.
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Hsu
authors.affiliation: Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan; Institute of Biochemistry and Biotechnology, Medical College, Chung-Shan Medical University, Taichung, Taiwan.
authors.forename: Yi-Hsien
authors.initials: YH
authors.lastname: Hsieh
authors.affiliation: Department of Life Science, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Ho
authors.initials: H
authors.lastname: Lin
authors.affiliation: Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan.
authors.forename: Jer-Yuh
authors.initials: JY
authors.lastname: Liu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D051571:Protein Kinase C-alpha / Q000096:biosynthesis* / Q000235:genetics; D017434:Protein Structure, Tertiary; D020218:Response Elements; D014158:Transcription, Genetic; D015854:Up-Regulation; D050807:ets-Domain Protein Elk-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C494112:ELK1 protein, human; D051741:Kruppel-Like Transcription Factors; C085969:MZF1 protein, human; D046912:Multiprotein Complexes; D050807:ets-Domain Protein Elk-1; C496628:PRKCA protein, human; D051571:Protein Kinase C-alpha