title: Targeting cyclin D1 in non-small cell lung cancer and mesothelioma cells by antisense oligonucleotides.
abstract: BACKGROUND
  Cyclin D1 overexpression exists in multiple types of cancer and is a potential chemopreventive or therapeutic target.
  
  
  METHODS
  Non-small cell lung cancer and mesothelioma cells were incubated with antisense oligonucleotides (ASO) to cyclin D1 (CD1) and evaluated for effects on cellular proliferation, apoptosis, expression of cell cycle-specific proteins, and protein phosphorylation states.
  
  
  RESULTS
  ASO to CD1 inhibited proliferation of non-small lung cancer cells and mesothelioma cells. ASO induced apoptosis as determined by TUNEL assay. Western blot analysis of cell lysate showed that ASO inhibited the de novo synthesis of CD1, CD3, and CDK2 in multiple cell lines. Immunoprecipitation and immunoblotting with phosphoantibodies demonstrated that CD1, CD3, and CDK2 exist in a phosphorylated state.
  
  
  CONCLUSIONS
  The work demonstrates that non-small cell lung cancer and mesothelioma cells respond to ASO-mediated cellular growth inhibition. These findings make ASO to CD1 attractive as a potential therapeutic for mesothelioma and non-small cell lung cancer.
authors: VA Medical Center, Section of Hematology/Oncology, Primary Care Service Line, Minneapolis, MN 55417, USA.
authors: Shamsher S
authors: SS
authors: Saini
authors: Mark A
authors: MA
authors: Klein
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D047468:Immunoprecipitation; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008654:Mesothelioma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010766:Phosphorylation; D014407:Tumor Cells, Cultured
chemical_list: C530104:CCND1 protein, human; D018797:Cell Cycle Proteins; D016376:Oligonucleotides, Antisense; D019938:Cyclin D1