This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Mesotheliomas are tumors that form in the mesothelial lining of the peritoneal, pleural or pericardial cavities. There is a strong tie to asbestos exposure, with tumors arising in 10% exposed workers and a history of asbestos exposure in about 70% to 80% of all patients with mesothelioma. Tumors form through poorly understood mechanisms involving a small number of genetic lesions, allowing escape from normal cellular growth control. Published reports strongly implicate a small set of tumor suppressor genes or oncogenes involved in regulating normal cellular growth: specifically the retinoblastoma (Rb) gene, the p53 gene, p16 and p14/ARF genes, and the neurofibromatosis 2 gene (NF2). NF2 and p16/p14ARF are consistently inactivated by mutations in the DNA, while p53 and RB suffer few mutations, but are inactivated by other mechanisms. In addition, a transforming DNA tumor virus, SV40, is thought to play a role in tumor formation. We hope to better understand the role of two of these genes in inactivating p53: SV40 Large T antigen (Tag), and NF2. Our hypothesis is that both genes effectively target the p53 gene for inactivation. Our study design involves creation of in vitro and in vivo models of tumor formation. These models involve either the induction of SV40 Tag expression in normal mouse lung via a viral delivery system or the study of asbestos-induced tumor formation in NF2 knockout mice. We will readout the results of these genetic changes by cellular transformation assays in in vitro models or tumor incidence in animal models.
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| Ward, Tony J; Semmens, Erin O; Weiler, Emily et al. (2017) Efficacy of interventions targeting household air pollution from residential wood stoves. J Expo Sci Environ Epidemiol 27:64-71 |
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| Gábriel, Robert; Erdélyi, Ferenc; Szabó, Gábor et al. (2016) Ectopic transgene expression in the retina of four transgenic mouse lines. Brain Struct Funct 221:3729-41 |
| Wang, Xiaobo; Olson, Jenessa R; Rasoloson, Dominique et al. (2016) Dynein light chain DLC-1 promotes localization and function of the PUF protein FBF-2 in germline progenitor cells. Development 143:4643-4653 |
| Yi, Feng; DeCan, Evan; Stoll, Kurt et al. (2015) Muscarinic excitation of parvalbumin-positive interneurons contributes to the severity of pilocarpine-induced seizures. Epilepsia 56:297-309 |
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