title: Deficiency of CCAAT/enhancer binding protein family DNA binding prevents malignant conversion of adenoma to carcinoma in NNK-induced lung carcinogenesis in the mouse.
abstract: BACKGROUND
  The CCAAT/enhancer binding proteins (C/EBPs) play important roles in carcinogenesis of many tumors including the lung. Since multiple C/EBPs are expressed in lung, the combinatorial expression of these C/EBPs on lung carcinogenesis is not known.
  
  
  METHODS
  A transgenic mouse line expressing a dominant negative A-C/EBP under the promoter of lung epithelial Clara cell secretory protein (CCSP) gene in doxycycline dependent fashion was subjected to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung carcinogenesis bioassay in the presence and absence of doxycycline, and the effect of abolition of DNA binding activities of C/EBPs on lung carcinogenesis was examined.
  
  
  RESULTS
  A-C/EBP expression was found not to interfere with tumor development; however, it suppressed the malignant conversion of adenoma to carcinoma during NNK-induced lung carcinogenesis. The results suggested that Ki67 may be used as a marker for lung carcinomas in mouse.
  
  
  CONCLUSIONS
  The DNA binding of C/EBP family members can be used as a potential molecular target for lung cancer therapy.
authors.affiliation: Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. kimuras@mail.nih.gov
authors.forename: Shioko
authors.initials: S
authors.lastname: Kimura
authors.forename: Jorge
authors.initials: J
authors.lastname: Paiz
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yoneda
authors.forename: Taketomo
authors.initials: T
authors.lastname: Kido
authors.forename: Charles
authors.initials: C
authors.lastname: Vinson
authors.forename: Jerrold M
authors.initials: JM
authors.lastname: Ward
mesh_terms: D000236:Adenoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics*; D020287:In Situ Nick-End Labeling; D015994:Incidence; D019394:Ki-67 Antigen / Q000378:metabolism; D008175:Lung Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009602:Nitrosamines / Q000633:toxicity; D011650:Pulmonary Alveoli / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D022762:CCAAT-Enhancer-Binding Proteins; D019394:Ki-67 Antigen; D009602:Nitrosamines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone