Morris G F, Hoyle G W, Athas G B, Lei W H, Xu J, Morris C B, Friedman M
Tulane Cancer Center, Department of Pathology, USA.
J La State Med Soc. 1998 Apr;150(4):179-85.
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.
肺癌是美国癌症死亡的最常见原因。在编码p53肿瘤抑制蛋白的基因中的突变与肺部恶性肿瘤之间存在强烈的相关性。我们的目标是制备一种在外周肺上皮细胞中p53功能被破坏的转基因小鼠模型。为实现这一目标，从人表面活性蛋白C（SPC）启动子表达一种“显性负性”p53突变形式。从SPC启动子表达的显性负性p53将拮抗转基因动物II型肺泡上皮细胞和一些细支气管细胞中的野生型p53功能，从而促进肺癌的发展。这种动物模型应该对肺癌发生的研究以及对导致肺部肿瘤转化的因素的鉴定有用。
