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Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model
Ist Teil von
Cancer cell, 2003-09, Vol.4 (3), p.181-189
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2003
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
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.