| Autor: |
Ruizhong Wang, Brijesh Kumar, Poornima Bhat‐Nakshatri, Mayuri S. Prasad, Max H. Jacobsen, Gabriela Ovalle, Calli Maguire, George Sandusky, Trupti Trivedi, Khalid S. Mohammad, Theresa Guise, Narsimha R. Penthala, Peter A. Crooks, Jianguo Liu, Teresa Zimmers, Harikrishna Nakshatri |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
JCSM Rapid Communications, Vol 4, Iss 1, Pp 24-39 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2617-1619 |
| DOI: |
10.1002/rco2.23 |
| Popis: |
Abstract Background Loss of skeletal muscle volume and functional limitations are poor prognostic markers in breast cancer patients. Several molecular defects in skeletal muscle including reduced myoblast determination protein 1 (MyoD) levels and increased protein turn over due to enhanced proteosomal activity have been suggested as causes of skeletal muscle loss in cancer patients. However, it is unknown whether molecular defects in skeletal muscle are dependent on tumour aetiology. Methods We characterized functional and molecular defects of skeletal muscle in mouse mammary tumour virus (MMTV)‐Neu (Neu+) mice (n = 6–12), an animal model that represents HER2 + human breast cancer, and compared the results with well‐characterized luminal B breast cancer model MMTV‐PyMT (PyMT+). Functional studies such as grip strength, rotarod performance, and ex vivo muscle contraction were performed to measure the effects of cancer on skeletal muscle. Expression of muscle‐enriched genes and microRNAs as well as circulating cytokines/chemokines were measured. Because nuclear factor‐kappaB (NF‐κB) pathway plays a significant role in skeletal muscle defects, the ability of NF‐κB inhibitor dimethylaminoparthenolide (DMAPT) to reverse skeletal muscle defects was examined. Results Neu+ mice showed skeletal muscle defects similar to accelerated aging. Compared with age and sex‐matched wild type mice, Neu+ tumour‐bearing mice had lower grip strength (202 ± 6.9 vs. 179 ± 6.8 g grip force, P = 0.0069) and impaired rotarod performance (108 ± 12.1 vs. 30 ± 3.9 s, P |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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