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Development of thymic tumor in [LSL:KrasG12D; Pdx1-CRE] mice, an adverse effect associated with accelerated pancreatic carcinogenesis.
Liot, Sophie; El Kholti, Naïma; Balas, Jonathan; Genestier, Laurent; Verrier, Bernard; Valcourt, Ulrich; Lambert, Elise.
Afiliación
  • Liot S; Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique (LBTI), UMR CNRS 5305, Université Claude Bernard Lyon 1, Institut de Biologie et Chimie Des Protéines, 7, passage du Vercors, 69367, Lyon Cedex 07, France.
  • El Kholti N; Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique (LBTI), UMR CNRS 5305, Université Claude Bernard Lyon 1, Institut de Biologie et Chimie Des Protéines, 7, passage du Vercors, 69367, Lyon Cedex 07, France.
  • Balas J; Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique (LBTI), UMR CNRS 5305, Université Claude Bernard Lyon 1, Institut de Biologie et Chimie Des Protéines, 7, passage du Vercors, 69367, Lyon Cedex 07, France.
  • Genestier L; UR LIB « Lymphoma Immuno-Biology", Université Claude Bernard Lyon I, Lyon, France.
  • Verrier B; Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique (LBTI), UMR CNRS 5305, Université Claude Bernard Lyon 1, Institut de Biologie et Chimie Des Protéines, 7, passage du Vercors, 69367, Lyon Cedex 07, France.
  • Valcourt U; Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique (LBTI), UMR CNRS 5305, Université Claude Bernard Lyon 1, Institut de Biologie et Chimie Des Protéines, 7, passage du Vercors, 69367, Lyon Cedex 07, France.
  • Lambert E; Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique (LBTI), UMR CNRS 5305, Université Claude Bernard Lyon 1, Institut de Biologie et Chimie Des Protéines, 7, passage du Vercors, 69367, Lyon Cedex 07, France. elise.lambert@ibcp.fr.
Sci Rep ; 11(1): 15075, 2021 07 23.
Article en En | MEDLINE | ID: mdl-34302028
Pancreatic Ductal AdenoCarcinoma (PDAC) represents about 90% of pancreatic cancers. It is one of the most aggressive cancer, with a 5-year survival rate below 10% due to late diagnosis and poor therapeutic efficiency. This bad prognosis thus encourages intense research in order to better understand PDAC pathogenesis and molecular basis leading to the development of innovative therapeutic strategies. This research frequently involves the KC (LSL:KrasG12D;Pdx1-CRE) genetically engineered mouse model, which leads to pancreatic cancer predisposition. However, as frequently encountered in animal models, the KC mouse model also exhibits biases. Herein, we report a new adverse effect of KrasG12D mutation in KC mouse model. In our hands, 10% of KC mice developed clinical signs reaching pre-defined end-points between 100- and 150-days post-parturition, and associated with large thymic mass development. Histological and genetic analyses of this massive thymus enabled us (1) to characterize it as a highly proliferative thymic lymphoma and (2) to detect the unexpected recombination of the Lox-STOP-Lox cassette upstream KrasG12D allele and subsequent KRASG12D protein expression in all cells composing thymic masses. Finally, we highlighted that development of such thymic tumor was associated with accelerated pancreatic carcinogenesis, immune compartment disorganization, and in some cases, lung malignancies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Neoplasias del Timo / Transactivadores / Proteínas Proto-Oncogénicas p21(ras) / Proteínas de Homeodominio / Carcinogénesis Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Sci Rep Año: 2021 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Neoplasias del Timo / Transactivadores / Proteínas Proto-Oncogénicas p21(ras) / Proteínas de Homeodominio / Carcinogénesis Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Sci Rep Año: 2021 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido