A model of pulmonary adenocarcinoma in transgenic mice expressing the simian virus 40 T antigen driven by the rat Calbindin-D9K (CaBP9K) promoter

Lung cancer is the most frequent cause of cancer deaths. Its origin and dev elopment remain poorly understood, partly because of the lack of pertinent animal models. This study produced transgenic mice expressing the simian vi rus (SV) 40 T antigen (Tag) driven by a 1011 base-pair DNA fragment of the rat Calbindin-D9K (CaBP9K) promoter. All transgenic animals developed multi focal pulmonary tumours with pathological and ultrastructural features cons istent with adenocarcinomas. Using immunohistochemistry, northern blot or w estern blot, tumours were found to express the transcription factor TTF-1, as well as specific markers of the peripheral airway Clara cells (CC10) and alveolar type II cells (surfactant proteins A, B, C, and D). This model, w ith its similarities to human adenocarcinoma, should be useful not only for addressing the mechanisms underlying the development and progression of lu ng cancer, but also for testing new therapeutic approaches. Copyright (C) 2 001 John Wiley & Sons, Ltd.