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C/EBP alpha Is Up-regulated in a Subset of Hepatocellular Carcinomas and Plays a Role in Cell Growth and Proliferation

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  • Background &Amp
  • Aims: C/Ebp Alpha (Cebpa) Is A Putative Tumor Suppressor
  • However
  • Initial Results Indicated That Cebpa Was Up-Regulated In A Subset Of Human Hepatocellular Carcinomas
  • The Regulation And Function Of C/Ebp Alpha Was Investigated In Hcc Cell Lines To Clarify Its Role In
  • Methods: The Regulation Of C/Ebp Alpha Expression Was Studied By Quantitative Reverse Transcription-
  • Western Blotting
  • Immunohistochemistry
  • Methylation-Specific Pcr
  • And Chromatin Immunoprecipitation Assays
  • C/Ebp Alpha Expression Was Knocked-Down By Small Interfering Rna Or Short Hairpin Rna
  • Functional Assays Included Colony Formation
  • Methylthiotetrazole
  • Bromodeoxyuridine Incorporation
  • And Luciferase-Reporter Assays
  • Results: Cebpa Was Up-Regulated At Least 2-Fold In A Subset (Approximately 55%) Of Human Hccs Compar
  • None Of The Up-Regulated Samples Were Positive For Hepatitis C Infection
  • The Hcc Cell Lines Hep3B And Huh7 Expressed High
  • Plc/Prf/5 Intermediate
  • Hepg2 And Hcc-M Low Levels Of C/Ebp Alpha
  • Recapitulating The Pattern Of Expression Observed In Hccs
  • No Mutations Were Detected In The Cebp Alpha Gene In Hccs And Cell Lines
  • C/Ebp Alpha Was Localized To The Nucleus And Functional In Hep3B And Huh7 Cells
  • Knocking-Down Its Expression Reduced Target-Gene Expression
  • Colony Formation
  • And Cell Growth
  • Associated With A Decrease In Cyclin A And Cdk4 Concentrations And E2F Transcriptional Activity
  • Epigenetic Mechanisms Including Dna Methylation
  • And The Binding Of Acetylated Histone H3 To The Cebp Alpha Promoter-Regulated Cebpa Expression In Th
  • Conclusions: C/Ebp Alpha Is Up-Regulated In A Subset Of Hccs And Has Growth-Promoting Activities In
  • Novel Oncogenic Mechanisms Involving C/Ebp Alpha May Be Amenable To Epigenetic Regulation To Improve
  • Economics


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