Sexual Dimorphism of Skeletal Muscle in a Mouse Model of Breast Cancer: A Functional and Molecular Analysis
Breast cancer incidence in men is statistically rare; however, given the lack of screening in males, more advanced stages at initial diagnosis result in lower 5-year survival rates for men with breast cancer compared to women. A sexual dimorphism, with respect to the effect of tumor growth on cachex...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/14/11669 |
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| author | Lauren E. Rentz Marcella A. Whetsell Stuart A. Clayton Alan D. Mizener Ida Holásková Matthew G. Chapa Emily H. Hoblitzell Timothy D. Eubank Emidio E. Pistilli |
| author_facet | Lauren E. Rentz Marcella A. Whetsell Stuart A. Clayton Alan D. Mizener Ida Holásková Matthew G. Chapa Emily H. Hoblitzell Timothy D. Eubank Emidio E. Pistilli |
| author_sort | Lauren E. Rentz |
| collection | DOAJ |
| description | Breast cancer incidence in men is statistically rare; however, given the lack of screening in males, more advanced stages at initial diagnosis result in lower 5-year survival rates for men with breast cancer compared to women. A sexual dimorphism, with respect to the effect of tumor growth on cachexia incidence and severity, has also been reported across cancer types. The purpose of this study was to examine the sexual dimorphism of breast cancer as it pertains to skeletal muscle function and molecular composition. Using female and male transgenic PyMT mice, we tested the hypothesis that the isometric contractile properties and molecular composition of skeletal muscle would be differentially affected by breast tumors. PyMT tumor-bearing mice of each sex, corresponding to maximal tumor burden, were compared to their respective controls. RNA sequencing of skeletal muscle revealed different pathway alterations that were exclusive to each sex. Further, differentially expressed genes and pathways were substantially more abundant in female tumor mice, with only minimal dysregulation in male tumor mice, each compared to their respective controls. These differences in the transcriptome were mirrored in isometric contractile properties, with greater tumor-induced dysfunction in females than male mice, as well as muscle wasting. Collectively, these data support the concept of sexually dimorphic responses to cancer in skeletal muscle and suggest that these responses may be associated with the clinical differences in breast cancer between the sexes. The identified sex-dependent pathways within the muscle of male and female mice provide a framework to evaluate therapeutic strategies targeting tumor-associated skeletal muscle alterations. |
| first_indexed | 2024-03-11T00:59:45Z |
| format | Article |
| id | doaj.art-7dbee60481394004ae8873479712c4cf |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T00:59:45Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7dbee60481394004ae8873479712c4cf2023-11-18T19:43:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124141166910.3390/ijms241411669Sexual Dimorphism of Skeletal Muscle in a Mouse Model of Breast Cancer: A Functional and Molecular AnalysisLauren E. Rentz0Marcella A. Whetsell1Stuart A. Clayton2Alan D. Mizener3Ida Holásková4Matthew G. Chapa5Emily H. Hoblitzell6Timothy D. Eubank7Emidio E. Pistilli8Division of Exercise Physiology, Department of Human Performance, West Virginia University School of Medicine, Morgantown, WV 26506, USADivision of Exercise Physiology, Department of Human Performance, West Virginia University School of Medicine, Morgantown, WV 26506, USADivision of Exercise Physiology, Department of Human Performance, West Virginia University School of Medicine, Morgantown, WV 26506, USACancer Institute, West Virginia University School of Medicine, Morgantown, WV 26506, USAOffice of Statistics, West Virginia Agriculture and Forestry Experiment Station, Davis College of Agriculture, Natural Resources and Design, West Virginia University, Morgantown, WV 26506, USACancer Institute, West Virginia University School of Medicine, Morgantown, WV 26506, USADepartment of Microbiology, Immunology, and Cell Biology, West Virginia University School of Medicine, Morgantown, WV 26506, USACancer Institute, West Virginia University School of Medicine, Morgantown, WV 26506, USADivision of Exercise Physiology, Department of Human Performance, West Virginia University School of Medicine, Morgantown, WV 26506, USABreast cancer incidence in men is statistically rare; however, given the lack of screening in males, more advanced stages at initial diagnosis result in lower 5-year survival rates for men with breast cancer compared to women. A sexual dimorphism, with respect to the effect of tumor growth on cachexia incidence and severity, has also been reported across cancer types. The purpose of this study was to examine the sexual dimorphism of breast cancer as it pertains to skeletal muscle function and molecular composition. Using female and male transgenic PyMT mice, we tested the hypothesis that the isometric contractile properties and molecular composition of skeletal muscle would be differentially affected by breast tumors. PyMT tumor-bearing mice of each sex, corresponding to maximal tumor burden, were compared to their respective controls. RNA sequencing of skeletal muscle revealed different pathway alterations that were exclusive to each sex. Further, differentially expressed genes and pathways were substantially more abundant in female tumor mice, with only minimal dysregulation in male tumor mice, each compared to their respective controls. These differences in the transcriptome were mirrored in isometric contractile properties, with greater tumor-induced dysfunction in females than male mice, as well as muscle wasting. Collectively, these data support the concept of sexually dimorphic responses to cancer in skeletal muscle and suggest that these responses may be associated with the clinical differences in breast cancer between the sexes. The identified sex-dependent pathways within the muscle of male and female mice provide a framework to evaluate therapeutic strategies targeting tumor-associated skeletal muscle alterations.https://www.mdpi.com/1422-0067/24/14/11669cachexiamuscle wastingRNA sequencingmuscle functionfatigue |
| spellingShingle | Lauren E. Rentz Marcella A. Whetsell Stuart A. Clayton Alan D. Mizener Ida Holásková Matthew G. Chapa Emily H. Hoblitzell Timothy D. Eubank Emidio E. Pistilli Sexual Dimorphism of Skeletal Muscle in a Mouse Model of Breast Cancer: A Functional and Molecular Analysis International Journal of Molecular Sciences cachexia muscle wasting RNA sequencing muscle function fatigue |
| title | Sexual Dimorphism of Skeletal Muscle in a Mouse Model of Breast Cancer: A Functional and Molecular Analysis |
| title_full | Sexual Dimorphism of Skeletal Muscle in a Mouse Model of Breast Cancer: A Functional and Molecular Analysis |
| title_fullStr | Sexual Dimorphism of Skeletal Muscle in a Mouse Model of Breast Cancer: A Functional and Molecular Analysis |
| title_full_unstemmed | Sexual Dimorphism of Skeletal Muscle in a Mouse Model of Breast Cancer: A Functional and Molecular Analysis |
| title_short | Sexual Dimorphism of Skeletal Muscle in a Mouse Model of Breast Cancer: A Functional and Molecular Analysis |
| title_sort | sexual dimorphism of skeletal muscle in a mouse model of breast cancer a functional and molecular analysis |
| topic | cachexia muscle wasting RNA sequencing muscle function fatigue |
| url | https://www.mdpi.com/1422-0067/24/14/11669 |
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