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: Shioko Kimura, Jorge Paiz, Mitsuhiro Yoneda, Taketomo Kido, Charles Vinson, Jerrold M Ward
• Journal: Molecular cancer (Mol Cancer) Vol. 11 Pg. 90 (Dec 12 2012) ISSN: 1476-4598 [Electronic] England
• PMID: 23234329 (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

Topics

• 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)