Circadian Alterations Increase with Progression in a Patient-Derived Cell Culture Model of Breast Cancer
Circadian rhythm disruption can elicit the development of various diseases, including breast cancer. While studies have used cell lines to study correlations between altered circadian rhythms and cancer, these models have different genetic backgrounds and do not mirror the changes that occur with di...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Clocks & Sleep |
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| Online Access: | https://www.mdpi.com/2624-5175/3/4/42 |
| _version_ | 1827673360996237312 |
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| author | Hui-Hsien Lin Stephanie R. Taylor Michelle E. Farkas |
| author_facet | Hui-Hsien Lin Stephanie R. Taylor Michelle E. Farkas |
| author_sort | Hui-Hsien Lin |
| collection | DOAJ |
| description | Circadian rhythm disruption can elicit the development of various diseases, including breast cancer. While studies have used cell lines to study correlations between altered circadian rhythms and cancer, these models have different genetic backgrounds and do not mirror the changes that occur with disease development. Isogenic cell models can recapitulate changes across cancer progression. Hence, in this study, a patient-derived breast cancer model, the 21T series, was used to evaluate changes to circadian oscillations of core clock protein transcription as cells progress from normal to malignant states. Three cell lines were used: H16N2 (normal breast epithelium), 21PT (atypical ductal hyperplasia), and 21MT-1 (invasive metastatic carcinoma). The cancerous cells are both HER2+. We assessed the transcriptional profiles of two core clock proteins, BMAL1 and PER2, which represent a positive and negative component of the molecular oscillator. In the normal H16N2 cells, both genes possessed rhythmic mRNA oscillations with close to standard periods and phases. However, in the cancerous cells, consistent changes were observed: both genes had periods that deviated farther from normal and did not have an anti-phase relationship. In the future, mechanistic studies should be undertaken to determine the oncogenic changes responsible for the circadian alterations found. |
| first_indexed | 2024-03-10T04:22:46Z |
| format | Article |
| id | doaj.art-4e897bd2341e4c01a41c9f8d38b59539 |
| institution | Directory Open Access Journal |
| issn | 2624-5175 |
| language | English |
| last_indexed | 2024-03-10T04:22:46Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Clocks & Sleep |
| spelling | doaj.art-4e897bd2341e4c01a41c9f8d38b595392023-11-23T07:45:38ZengMDPI AGClocks & Sleep2624-51752021-11-013459860810.3390/clockssleep3040042Circadian Alterations Increase with Progression in a Patient-Derived Cell Culture Model of Breast CancerHui-Hsien Lin0Stephanie R. Taylor1Michelle E. Farkas2Department of Chemistry, University of Massachusetts Amherst, Amherst, MA 01003, USADepartment of Computer Science, Colby College, Waterville, ME 04901, USADepartment of Chemistry, University of Massachusetts Amherst, Amherst, MA 01003, USACircadian rhythm disruption can elicit the development of various diseases, including breast cancer. While studies have used cell lines to study correlations between altered circadian rhythms and cancer, these models have different genetic backgrounds and do not mirror the changes that occur with disease development. Isogenic cell models can recapitulate changes across cancer progression. Hence, in this study, a patient-derived breast cancer model, the 21T series, was used to evaluate changes to circadian oscillations of core clock protein transcription as cells progress from normal to malignant states. Three cell lines were used: H16N2 (normal breast epithelium), 21PT (atypical ductal hyperplasia), and 21MT-1 (invasive metastatic carcinoma). The cancerous cells are both HER2+. We assessed the transcriptional profiles of two core clock proteins, BMAL1 and PER2, which represent a positive and negative component of the molecular oscillator. In the normal H16N2 cells, both genes possessed rhythmic mRNA oscillations with close to standard periods and phases. However, in the cancerous cells, consistent changes were observed: both genes had periods that deviated farther from normal and did not have an anti-phase relationship. In the future, mechanistic studies should be undertaken to determine the oncogenic changes responsible for the circadian alterations found.https://www.mdpi.com/2624-5175/3/4/42breast cancercancer progressioncircadian rhythmmetastatic cellsrhythmicity |
| spellingShingle | Hui-Hsien Lin Stephanie R. Taylor Michelle E. Farkas Circadian Alterations Increase with Progression in a Patient-Derived Cell Culture Model of Breast Cancer Clocks & Sleep breast cancer cancer progression circadian rhythm metastatic cells rhythmicity |
| title | Circadian Alterations Increase with Progression in a Patient-Derived Cell Culture Model of Breast Cancer |
| title_full | Circadian Alterations Increase with Progression in a Patient-Derived Cell Culture Model of Breast Cancer |
| title_fullStr | Circadian Alterations Increase with Progression in a Patient-Derived Cell Culture Model of Breast Cancer |
| title_full_unstemmed | Circadian Alterations Increase with Progression in a Patient-Derived Cell Culture Model of Breast Cancer |
| title_short | Circadian Alterations Increase with Progression in a Patient-Derived Cell Culture Model of Breast Cancer |
| title_sort | circadian alterations increase with progression in a patient derived cell culture model of breast cancer |
| topic | breast cancer cancer progression circadian rhythm metastatic cells rhythmicity |
| url | https://www.mdpi.com/2624-5175/3/4/42 |
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