Circadian disruption does not alter tumorigenesis in a mouse model of lymphoma [version 2; peer review: 2 approved]
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...
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| Format: | Article |
| Language: | English |
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F1000 Research Ltd
2023-09-01
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| Series: | F1000Research |
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| Online Access: | https://f1000research.com/articles/12-49/v2 |
| _version_ | 1797663931630616576 |
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| author | Marie Pariollaud Katja A Lamia Rebecca M Mello |
| author_facet | Marie Pariollaud Katja A Lamia Rebecca M Mello |
| author_sort | Marie Pariollaud |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T19:21:57Z |
| format | Article |
| id | doaj.art-3d0fcd91667240a7bb67e160dd6c02cf |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-03-11T19:21:57Z |
| publishDate | 2023-09-01 |
| publisher | F1000 Research Ltd |
| record_format | Article |
| series | F1000Research |
| spelling | doaj.art-3d0fcd91667240a7bb67e160dd6c02cf2023-10-07T00:00:01ZengF1000 Research LtdF1000Research2046-14022023-09-0112156285Circadian disruption does not alter tumorigenesis in a mouse model of lymphoma [version 2; peer review: 2 approved]Marie Pariollaud0https://orcid.org/0000-0003-2325-6394Katja A Lamia1https://orcid.org/0000-0001-9533-0499Rebecca M Mello2Molecular Medicine, Scripps Research Institute, La Jolla, CA, 92037, USAMolecular Medicine, Scripps Research Institute, La Jolla, CA, 92037, USAMolecular Medicine, Scripps Research Institute, La Jolla, CA, 92037, USABackground: 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.https://f1000research.com/articles/12-49/v2c-MYC circadian rhythm lymphoma circadian disruption chronic jetlag CRY2eng |
| spellingShingle | Marie Pariollaud Katja A Lamia Rebecca M Mello Circadian disruption does not alter tumorigenesis in a mouse model of lymphoma [version 2; peer review: 2 approved] F1000Research c-MYC circadian rhythm lymphoma circadian disruption chronic jetlag CRY2 eng |
| title | Circadian disruption does not alter tumorigenesis in a mouse model of lymphoma [version 2; peer review: 2 approved] |
| title_full | Circadian disruption does not alter tumorigenesis in a mouse model of lymphoma [version 2; peer review: 2 approved] |
| title_fullStr | Circadian disruption does not alter tumorigenesis in a mouse model of lymphoma [version 2; peer review: 2 approved] |
| title_full_unstemmed | Circadian disruption does not alter tumorigenesis in a mouse model of lymphoma [version 2; peer review: 2 approved] |
| title_short | Circadian disruption does not alter tumorigenesis in a mouse model of lymphoma [version 2; peer review: 2 approved] |
| title_sort | circadian disruption does not alter tumorigenesis in a mouse model of lymphoma version 2 peer review 2 approved |
| topic | c-MYC circadian rhythm lymphoma circadian disruption chronic jetlag CRY2 eng |
| url | https://f1000research.com/articles/12-49/v2 |
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