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 development remain poorly understood, partly because of the lack of pertinent animal models. This study produced transgenic mice expressing the simian virus (SV) 40 T antigen (Tag) driven by a 1011 base-pair DNA fragment of the rat Calbindin-D9K (CaBP9K) promoter. All transgenic animals developed multifocal pulmonary tumours with pathological and ultrastructural features consistent with adenocarcinomas. Using immunohistochemistry, northern blot or western 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, with its similarities to human adenocarcinoma, should be useful not only for addressing the mechanisms underlying the development and progression of lung cancer, but also for testing new therapeutic approaches.
Chailley-Heu
B
B
INSERM Unité 319, Université Paris 7/Denis Diderot, 2 Place Jussieu, 75251, Paris Cedex 05, France.
Rambaud
C
C
Barlier-Mur
A M
AM
Galateau-Salle
F
F
Perret
C
C
Capron
F
F
Lacaze-Masmonteil
T
T
D000230:Adenocarcinoma / Q000235:genetics*; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D015152:Blotting, Northern; D015153:Blotting, Western; D064026:Calbindins; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism; D004195:Disease Models, Animal; D008175:Lung Neoplasms / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011506:Proteins / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism; D051381:Rats; D064030:S100 Calcium Binding Protein G / Q000235:genetics*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014598:Uteroglobin
D000952:Antigens, Polyomavirus Transforming; D064026:Calbindins; D053379:Chromogranin A; D002864:Chromogranins; C000614412:NKX2-1 protein, human; C000614414:Nkx2-1 protein, mouse; C000614416:Nkx2-1 protein, rat; D009687:Nuclear Proteins; D011506:Proteins; D011663:Pulmonary Surfactants; D064030:S100 Calcium Binding Protein G; C576506:S100G protein, human; C576507:S100g protein, mouse; C576508:S100g protein, rat; C556389:SCGB1A1 protein, human; C556390:Scgb1a1 protein, mouse; C556391:Scgb1a1 protein, rat; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D014598:Uteroglobin