دورية أكاديمية
Circadian disruption does not alter tumorigenesis in a mouse model of lymphoma [version 2; peer review: 2 approved]
| العنوان: | Circadian disruption does not alter tumorigenesis in a mouse model of lymphoma [version 2; peer review: 2 approved] |
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| المؤلفون: | Marie Pariollaud, Katja A Lamia, Rebecca M Mello |
| المصدر: | F1000Research, Vol 12 (2023) |
| بيانات النشر: | F1000 Research Ltd, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | c-MYC, circadian rhythm, lymphoma, circadian disruption, chronic jetlag, CRY2, eng, Medicine, Science |
| الوصف: | Background: Disruption of natural light cycles, as experienced by shift workers, is linked to enhanced cancer incidence. Several mouse models of cancer develop more severe disease when exposed to irregular light/dark cycles, supporting the connection between circadian disruption and increased cancer risk. Cryptochrome 2 (CRY2), a repressive component of the molecular circadian clock, facilitates turnover of the oncoprotein c-MYC, one mechanism that may link the molecular clock to tumorigenesis. In Eμ-MYC mice, which express transgenic c-MYC in B cells and develop aggressive lymphomas and leukemia, global Cry2 deletion reduces survival and enhances tumor formation. Lighting conditions that mimic the disruption experienced by shift workers dampen Cry2 transcripts in peripheral tissues of C57BL/6J mice. Although it is milder than homozygous deletion of Cry2, we hypothesized that reduced Cry2 rhythmicity could alter MYC protein accumulation and contribute to enhanced cancer risk caused by circadian disruption. We tested this hypothesis in MYC-driven lymphoma. Methods: We housed Eμ-MYC mice in light-tight boxes set to either control (continuous cycles of 12-hours of light followed by 12-hours of dark, LD12:12) or chronic jetlag (eight-hour light phase advances every two to three days, CJL) lighting conditions and assessed the impact of disrupted light cycles on survival and tumor formation in Eμ-MYC mice. Results: Environmental disruption of circadian rhythms did not alter tumor location, tumor growth, or survival in Eμ-MYC mice. Conclusions: Dampened rhythms of Cry2 following disruption of circadian light exposures is milder than deletion of Cry2. The lack of phenotype caused by altered circadian gene expression in contrast to enhanced tumorigenesis caused by homozygous deletion of Cry2 suggests that CRY2 dosage impacts this model. Importantly, these findings indicate that increased cancer risk associated with circadian disruption arises from one or more mechanisms that are not recapitulated here, and may be different in distinct tumor types. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2046-1402 91667240 |
| Relation: | https://f1000research.com/articles/12-49/v2; https://doaj.org/toc/2046-1402 |
| DOI: | 10.12688/f1000research.125272.2 |
| URL الوصول: | https://doaj.org/article/3d0fcd91667240a7bb67e160dd6c02cf |
| رقم الأكسشن: | edsdoj.3d0fcd91667240a7bb67e160dd6c02cf |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20461402 91667240 |
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| DOI: | 10.12688/f1000research.125272.2 |