Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model.
Small cell lung cancer (SCLC) is a highly aggressive human tumor with a more than 95% mortality rate. Its ontogeny and molecular pathogenesis remains poorly understood. We established a mouse model for neuroendocrine (NE) lung tumors by conditional inactivation of Rb1 and Trp53 in mouse lung epithelial cells. Mice carrying conditional alleles for both Rb1 and Trp53 developed with high incidence aggressive lung tumors with striking morphologic and immunophenotypic similarities to SCLC. Most of these tumors, which we designate MSCLC (murine small cell lung carcinoma), diffusely spread through the lung and gave rise to extrapulmonary metastases. In our model, inactivation of both Rb1 and p53 was a prerequisite for the pathogenesis of SCLC.
Meuwissen
Ralph
R
Division of Molecular Genetics and Center of Biomedical Genetics, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Linn
Sabine C
SC
Linnoila
R Ilona
RI
Zevenhoven
John
J
Mooi
Wolter J
WJ
Berns
Anton
A
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D018288:Carcinoma, Small Cell / Q000209:etiology / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D016158:Genes, p53 / Q000235:genetics* / Q000502:physiology; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D016160:Retinoblastoma Protein / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C499317:Ascl1 protein, mouse