High-density oligonucleotide microarrays and functional network analysis reveal extended lung carcinogenesis pathway maps and multiple interacting genes in NNK [4-(methylnitrosamino)-1-(3-pyridyle)-1-butanone] induced CD1 mouse lung tumor.

Abstract

PURPOSE:

NNK [4-(methylnitrosamino)-1-(3-pyridyle)-1-butanone] is a nicotine-derived nitrosaminoketone contained in tobacco smoke used as a powerful chemical carcinogen for rodent experimental models of pulmonary carcinogenesis. To clarify its carcinogenetic mechanisms, we examined the expression status of 22,625 mouse genes.

METHODS:

The affymetrix GeneChip mouse expression 430 A arrays have been used in CD1-induced mouse lung tumor. The affected genes were analyzed by Ingenuity pathway analysis to investigate functional network and gene ontology.

RESULTS:

A total of 876 genes were found to be differentially expressed at least twofold between NNK-induced tumors and normal lung tissues, 390 up-regulated and 486 down-regulated in these lesions. The functions with the highest P values were related to cellular growth and proliferation (P = 1.71 x 10(-4) to 4.10 x 10(-2)). In addition, we identified canonical pathways for Wnt/beta-catenin signaling (P = 0.0338).

CONCLUSIONS:

These results suggest that application of gene expression profiling may provide an improved strategy for therapeutic targeting of tobacco smoking-induced lung cancer.

• Authors: Hekmat Osman Abdel-Aziz, Ichiro Takasaki, Yoshiaki Tabuchi, Kazuhiro Nomoto, Yoshihiro Murai, Koichi Tsuneyama, Yasuo Takano
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 133 Issue 2 Pg. 107-15 (Feb 2007) ISSN: 0171-5216 [Print] Germany
• PMID: 16977459 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carcinogens
• Nitrosamines
• 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone

Topics

• Animals
• Carcinogens (toxicity)
• Cell Line, Tumor
• Cell Transformation, Neoplastic (genetics)
• Female
• Gene Expression Profiling
• Gene Regulatory Networks (drug effects)
• Lung Neoplasms (chemically induced, genetics, pathology)
• Mice
• Mice, Inbred Strains
• Models, Animal
• Models, Biological
• Nitrosamines (toxicity)
• Oligonucleotide Array Sequence Analysis
• Signal Transduction