Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Tamoxifen treatment of MCF-7 breast cancer cells

ABSTRACT: Tamoxifen is an anti-estrogen drug used in the treatment of Estrogen Receptor (ER) positive breast cancer. Effects and side effects of tamoxifen is the sum of tamoxifen and all its metabolites. Using concentrations that mimic the clinical situation we examined effects of 4OHtam, 4OHNDtam and NDtam on global gene expression in 17beta-estradiol (E2) treated MCF-7 cells.

ORGANISM(S): Homo sapiens

SUBMITTER: Rita Holdhus

PROVIDER: E-MTAB-2729 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The active tamoxifen metabolite endoxifen (4OHNDtam) strongly down-regulates cytokeratin 6 (CK6) in MCF-7 breast cancer cells.

Helland Thomas T Gjerde Jennifer J Dankel Simon S Fenne Ingvild S IS Skartveit Linn L Drangevåg Andreas A Bozickovic Olivera O Flågeng Marianne Hauglid MH Søiland Håvard H Mellgren Gunnar G Lien Ernst A EA

PloS one 20150413 4

<h4>Introduction</h4>Tamoxifen is an anti-estrogen drug used in treatment of Estrogen Receptor (ER) positive breast cancer. Effects and side effects of tamoxifen is the sum of tamoxifen and all its metabolites. 4-Hydroxytamoxifen (4OHtam) and 4-hydroxy-N-demethyltamoxifen (4OHNDtam, endoxifen) both have ER affinity exceeding that of the parent drug tamoxifen. 4OHNDtam is considered the main active metabolite of tamoxifen. Ndesmethyltamoxifen (NDtam) is the major tamoxifen metabolite. It has low ...[more]

PMID: 25867603

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Project 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.

Dataset Information

Tamoxifen treatment of MCF-7 breast cancer cells

Publications

The active tamoxifen metabolite endoxifen (4OHNDtam) strongly down-regulates cytokeratin 6 (CK6) in MCF-7 breast cancer cells.

Similar Datasets

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