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

Molecular Cancer

Research

Jerrold M Ward¹  Mitsuhiro Yoneda²  Shioko Kimura²  Jorge Paiz²  Taketomo Kido²  Charles Vinson² 

[1] Global VetPathology, Montgomery Village, 20866, Maryland, USA;Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, 20892, Bethesda, Maryland, USA;

关键词: C/EBPs;    Lung chemical carcinogenesis bioassay;    Dominant negative;    A-C/EBP;    Transgenic mouse;    4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone;    NNK;   

DOI  :  10.1186/1476-4598-11-90

 received in 2012-08-24, accepted in 2012-12-10,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsA 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.ResultsA-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.ConclusionsThe DNA binding of C/EBP family members can be used as a potential molecular target for lung cancer therapy.

【 授权许可】

CC BY   
© Kimura et al.; licensee BioMed Central Ltd. 2012