Development of thymic tumor in [LSL:Kras G12D ; Pdx1-CRE] mice, an adverse effect associated with accelerated pancreatic carcinogenesis
Abstract 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 un...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-94566-x |
| _version_ | 1818858483563364352 |
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| author | Sophie Liot Naïma El Kholti Jonathan Balas Laurent Genestier Bernard Verrier Ulrich Valcourt Elise Lambert |
| author_facet | Sophie Liot Naïma El Kholti Jonathan Balas Laurent Genestier Bernard Verrier Ulrich Valcourt Elise Lambert |
| author_sort | Sophie Liot |
| collection | DOAJ |
| description | Abstract 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:Kras G12D ;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 Kras G12D 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 Kras G12D 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. |
| first_indexed | 2024-12-19T08:57:00Z |
| format | Article |
| id | doaj.art-9b7de59685214b748379263377f07ace |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T08:57:00Z |
| publishDate | 2021-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-9b7de59685214b748379263377f07ace2022-12-21T20:28:35ZengNature PortfolioScientific Reports2045-23222021-07-0111111210.1038/s41598-021-94566-xDevelopment of thymic tumor in [LSL:Kras G12D ; Pdx1-CRE] mice, an adverse effect associated with accelerated pancreatic carcinogenesisSophie Liot0Naïma El Kholti1Jonathan Balas2Laurent Genestier3Bernard Verrier4Ulrich Valcourt5Elise Lambert6Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique (LBTI), UMR CNRS 5305, Université Claude Bernard Lyon 1, Institut de Biologie et Chimie Des ProtéinesLaboratoire de Biologie Tissulaire et Ingénierie Thérapeutique (LBTI), UMR CNRS 5305, Université Claude Bernard Lyon 1, Institut de Biologie et Chimie Des ProtéinesLaboratoire de Biologie Tissulaire et Ingénierie Thérapeutique (LBTI), UMR CNRS 5305, Université Claude Bernard Lyon 1, Institut de Biologie et Chimie Des ProtéinesUR LIB « Lymphoma Immuno-Biology”, Université Claude Bernard Lyon ILaboratoire de Biologie Tissulaire et Ingénierie Thérapeutique (LBTI), UMR CNRS 5305, Université Claude Bernard Lyon 1, Institut de Biologie et Chimie Des ProtéinesLaboratoire de Biologie Tissulaire et Ingénierie Thérapeutique (LBTI), UMR CNRS 5305, Université Claude Bernard Lyon 1, Institut de Biologie et Chimie Des ProtéinesLaboratoire de Biologie Tissulaire et Ingénierie Thérapeutique (LBTI), UMR CNRS 5305, Université Claude Bernard Lyon 1, Institut de Biologie et Chimie Des ProtéinesAbstract 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:Kras G12D ;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 Kras G12D 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 Kras G12D 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.https://doi.org/10.1038/s41598-021-94566-x |
| spellingShingle | Sophie Liot Naïma El Kholti Jonathan Balas Laurent Genestier Bernard Verrier Ulrich Valcourt Elise Lambert Development of thymic tumor in [LSL:Kras G12D ; Pdx1-CRE] mice, an adverse effect associated with accelerated pancreatic carcinogenesis Scientific Reports |
| title | Development of thymic tumor in [LSL:Kras G12D ; Pdx1-CRE] mice, an adverse effect associated with accelerated pancreatic carcinogenesis |
| title_full | Development of thymic tumor in [LSL:Kras G12D ; Pdx1-CRE] mice, an adverse effect associated with accelerated pancreatic carcinogenesis |
| title_fullStr | Development of thymic tumor in [LSL:Kras G12D ; Pdx1-CRE] mice, an adverse effect associated with accelerated pancreatic carcinogenesis |
| title_full_unstemmed | Development of thymic tumor in [LSL:Kras G12D ; Pdx1-CRE] mice, an adverse effect associated with accelerated pancreatic carcinogenesis |
| title_short | Development of thymic tumor in [LSL:Kras G12D ; Pdx1-CRE] mice, an adverse effect associated with accelerated pancreatic carcinogenesis |
| title_sort | development of thymic tumor in lsl kras g12d pdx1 cre mice an adverse effect associated with accelerated pancreatic carcinogenesis |
| url | https://doi.org/10.1038/s41598-021-94566-x |
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