ERBB2-induced inflammation in lung carcinogenesis.

ERBB2/HER2/NEU, a member of the epidermal growth factor receptor family, is overexpressed in more than 25 % of non-small cell lung cancer and is considered to be a significant and independent prognostic factor in lung cancer. Here we generated a lung specific HER2 overexpressing transgenic mouse model. In this model, HER2 was driven by the human surfactant protein-C promoter to investigate the role of the HER2 oncogene in pulmonary carcinogenesis and progression. Notably, significant pathological changes, including lymphocyte infiltration and mesenchymal cells hyperplasia, were found in the lung tissue of transgenic mice aged from 4 to 12 months. The occurrence and severity of those lesions increased as the mice aged. Some inflammatory factors, such as tumor necrosis factor, interleukin 1 and interleukin 6, were upregulated in lung tissue of transgenic mice compared with that of wild-type mice, implying that long-term HER2 overexpression could induce serious lung inflammation and some precancerous lesions. This model would be useful for studying the mechanism of HER2 involvement in lung carcinogenesis and for understanding the relationship between carcinogenesis and inflammation.