Lung-specific expression in mice of a dominant negative mutant form of the p53 tumor suppressor protein

Lung cancer is the most frequent cause of cancer deaths in the United States. A strong correlation exists between mutations in the gene encoding the p53 tumor suppressor protein and lung malignancies. Our goal is to prepare a transgenic mouse model with disrupted p53 function in the epithelial cells of the peripheral lung. To achieve this goal, a "dominant negative" mutant form of p53 was expressed from the human surfactant protein C (SPC) promoter. The dominant negative p53 expressed from the SPC promoter will antagonize wild-type p53 functions in alveolar type II pneumocytes and some bronchiolar cells of the transgenic animals and thereby promote development of carcinoma of the lung. This animal model should prove useful to the study of lung carcinogenesis and to the identification of agents that contribute to neoplastic conversion in the lung.