PXD042803
PXD042803 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | The Effect of Tamoxifen on Proteome Expression During in vitro Myogenesis in Murine Skeletal Muscle C2C12 Cells |
| Description | Tamoxifen, a selective estrogen receptor modulator (SERM), is commonly used in the treatment of hormone-responsive cancers. The effects of tamoxifen in anabolic tissues harboring estrogen-receptors, such as skeletal muscle, are poorly understood. As estrogen and estrogen receptors play an important role in skeletal muscle development and repair, we hypothesize that tamoxifen may have specific effects on myogenesis, the developmental process underlying muscle cells differentiation and repair. Myogenesis is characterized by fine-tuned changes in protein expression as embryonic myoblasts and adult satellite cells transition from pluripotent stem cells to multinucleated, contractile muscle fibers: we undertake a quantitative proteomic analysis of tamoxifen-induced changes in developing skeletal muscle cells which we expect may also shed light on the effect of tamoxifen on muscle repair. We report a tandem mass-tag (TMT) approach to tamoxifen-treated myogenesis in C2C12 cells, a well-characterized model of in vitro murine skeletal muscle differentiation. A longitudinal analysis of >10,000 proteins identified in C2C12 myogenesis revealed a novel subset of 1,239 myogenically-regulated proteins. This set of regulatory proteins clustered into five distinct longitudinal expression trends which significantly overlap those obtained in similar analyses performed in human myocytes. A longitudinal analysis of myogenesis in the presence of tamoxifen, when contrasted with a similar analysis in untreated myogenesis finds that while the vast majority of myogenically-regulated proteins were unaffected by tamoxifen treatment, specific pathways and networks are affected. We document a specific functional enrichment for adiponectin-signaling, whereby a set of 198 proteins were differentially expressed relative to controls at one or more stages of myogenesis, the majority of which were involved in steroid biosynthesis, lipid storage and/or metal ion homeostasis. Interestingly, the only protein that was differentially expressed in the tamoxifen-treated cells at every stage of myogenesis was metallothionein-1 (MT1). Elevated levels of MT1 have been correlated with tamoxifen resistance and increased patient mortality and relapse in breast cancer, as well as with cachexia and muscle atrophy in rodent models. Increased MT1 expression levels may contribute to the musculoskeletal effects reported by patients undergoing tamoxifen treatment. Finally, we present a powerful, self-validating pipeline for analyzing the total proteomic response to in vitro treatment across every stage of muscle cells development which can be easily adapted to study the effects of other drugs on myogenesis. |
| HostingRepository | MassIVE |
| AnnounceDate | 2023-09-06 |
| AnnouncementXML | Submission_2023-09-06_09:33:44.732.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Mark Adamo |
| SpeciesList | scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090; |
| ModificationList | Carbamidomethyl; Oxidation; TMT6plex |
| Instrument | Orbitrap Fusion |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2023-06-07 12:00:01 | ID requested | |
| ⏵ 1 | 2023-09-06 09:33:45 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: tamoxifen, myogenesis, SERM, anabolic, estrogen, muscle, C2C12, adiponectin, MT1, steroid |
Contact List
| Stylianos P. Scordilis | |
|---|---|
| contact affiliation | Smith College |
| contact email | sscordil@science.smith.edu |
| lab head | |
| Mark Adamo | |
| contact affiliation | Dartmouth College |
| contact email | mark.e.adamo@dartmouth.edu |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive.ucsd.edu/MSV000092126/ |
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