title: Ectopic ERK expression induces phenotypic conversion of C10 cells and alters DNA methyltransferase expression.
abstract: BACKGROUND
  Many lung carcinogens activate mitogen activated protein kinase (MAPK) pathways and DNA methyltransferases (DNMTs) are under investigation as therapeutic targets for lung cancer. Our goal is to determine whether C10 type II alveolar epithelial cells are a sensitive model to investigate ERK-dependent transformation and DNMT expression patterns in experimental lung cancer.
  
  
  RESULTS
  Ectopic expression of an extracellular signal regulated kinase (ERK)-green fluorescent protein (ERK1-GFP) induces acquisition of growth in soft agar that is selectively associated with latent effects on the expression of DNA methyl transferases (DNMT1 and 3b), xeroderma pigmentosum complementation group A (XPA), DNA-dependent protein kinase catalytic subunit (DNA-PKcs), increased phosphatase activity and enhanced sensitivity to 5-azacytidine (5-azaC)-mediated toxicity, relative to controls.
  
  
  CONCLUSIONS
  Ectopic expression of ERK alone is sufficient to promote phenotypic conversion of C10 cells associated with altered DNMT expression patterns and sensitivity to DNMT inhibitor. This model may have applications for predicting sensitivity to DNMT inhibitors.
authors.affiliation: Systems Toxicology, Pacific Northwest National Laboratory, 790 6th Street, J4-02, Richland, WA 99354, USA.
authors.forename: Ryan L
authors.initials: RL
authors.lastname: Sontag
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Weber
mesh_terms: D056809:Alveolar Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002457:Cell Extracts; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D051747:DNA-Activated Protein Kinase / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D051379:Mice; D010641:Phenotype; D014161:Transduction, Genetic; D051760:Xeroderma Pigmentosum Group A Protein / Q000378:metabolism; D000097584:DNA Methyltransferase 3B
chemical_list: D001374:Azacitidine; D002457:Cell Extracts; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D051747:DNA-Activated Protein Kinase; D048049:Extracellular Signal-Regulated MAP Kinases; D049452:Green Fluorescent Proteins; D006655:Histone Deacetylases; D051760:Xeroderma Pigmentosum Group A Protein; D000097584:DNA Methyltransferase 3B; C000619381:Dnmt1 protein, mouse