A conditional mouse model for malignant mesothelioma.
Malignant mesothelioma is a devastating disease that has been associated with loss of Neurofibromatosis type 2 (NF2) and genetic lesions affecting RB and P53 pathways. We introduced similar lesions in the mesothelial lining of the thoracic cavity of mice. Mesothelioma developed at high incidence in Nf2;Ink4a/Arf and Nf2;p53 conditional knockout mice with median survival times of approximately 30 and 20 weeks, respectively. Murine mesothelioma closely mimicked human malignant mesothelioma. Conditional Nf2;Ink4a/Arf mice showed increased pleural invasion compared to conditional Nf2;p53 mice. Interestingly, upon Ink4a loss in the latter mice median survival was significantly reduced and all tumors were highly invasive, suggesting that Ink4a loss substantially contributes to the poor clinical outcome of malignant mesothelioma.
Jongsma
Johan
J
Department of Molecular Genetics, Cancer Genomics Centre, Centre for Biomedical Genetics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
van Montfort
Erwin
E
Vooijs
Marc
M
Zevenhoven
John
J
Krimpenfort
Paul
P
van der Valk
Martin
M
van de Vijver
Marc
M
Berns
Anton
A
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D015622:Epithelioid Cells / Q000378:metabolism / Q000473:pathology; D005822:Genetic Vectors; D005838:Genotype; D007150:Immunohistochemistry; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D019656:Loss of Heterozygosity; D008163:Luminescent Measurements; D008654:Mesothelioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D018198:Mixed Tumor, Malignant / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016518:Neurofibromatosis 2 / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011995:Recombination, Genetic; D012509:Sarcoma / Q000378:metabolism / Q000473:pathology; D035423:Thoracic Cavity / Q000378:metabolism* / Q000473:pathology; D013899:Thoracic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D019941:Cyclin-Dependent Kinase Inhibitor p16; D016159:Tumor Suppressor Protein p53; C045073:Cre recombinase; D019426:Integrases