Deficiency of CCAAT/enhancer binding protein family DNA binding prevents malignant conversion of adenoma to carcinoma in NNK-induced lung carcinogenesis in the mouse.

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.
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.
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.
The DNA binding of C/EBP family members can be used as a potential molecular target for lung cancer therapy.
AuthorsShioko Kimura, Jorge Paiz, Mitsuhiro Yoneda, Taketomo Kido, Charles Vinson, Jerrold M Ward
JournalMolecular cancer (Mol Cancer) Vol. 11 Pg. 90 ( 2012) ISSN: 1476-4598 [Electronic] England
PMID23234329 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
Chemical References
  • Biomarkers, Tumor
  • CCAAT-Enhancer-Binding Proteins
  • Ki-67 Antigen
  • Nitrosamines
  • 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
  • Adenoma (epidemiology, genetics, pathology)
  • Animals
  • Biomarkers, Tumor (metabolism)
  • CCAAT-Enhancer-Binding Proteins (deficiency, genetics, metabolism)
  • Carcinoma (epidemiology, genetics, pathology)
  • Cell Transformation, Neoplastic (chemically induced, genetics)
  • In Situ Nick-End Labeling
  • Incidence
  • Ki-67 Antigen (metabolism)
  • Lung Neoplasms (chemically induced, epidemiology, genetics, pathology)
  • Male
  • Mice
  • Mice, Transgenic
  • Nitrosamines (toxicity)
  • Pulmonary Alveoli (pathology)

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