Sphingosine kinase isoforms as a therapeutic target in endocrine therapy resistant luminal and basal-A breast cancer
| Autor: | James W. Antoon, Matthew E. Burow, Martin D. White, Jennifer L. Driver, Barbara S. Beckman |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Ceramide
Antineoplastic Agents Hormonal Pyridines Sphingosine kinase Mice Nude Adamantane Breast Neoplasms Enzyme-Linked Immunosorbent Assay Mice SCID Biology Aminophenols Real-Time Polymerase Chain Reaction General Biochemistry Genetics and Molecular Biology Article chemistry.chemical_compound Mice Breast cancer In vivo Cell Line Tumor medicine Animals Humans Sphingosine-1-phosphate Enzyme Inhibitors skin and connective tissue diseases DNA Primers Base Sequence Cancer medicine.disease Sphingolipid Xenograft Model Antitumor Assays Isoenzymes Phosphotransferases (Alcohol Group Acceptor) Thiazoles chemistry Receptors Estrogen Apoptosis Drug Resistance Neoplasm Immunology Cancer research Female |
| Zdroj: | Experimental biology and medicine (Maywood, N.J.). 237(7) |
| ISSN: | 1535-3699 |
| Popis: | Sphingosine kinase signaling has become of increasing interest as a cancer target in recent years. Two sphingosine kinase inhibitors, sphingosine kinase inhibitor (SKI)-II and ABC294640, are promising as potential breast cancer therapies. However, evidence for their therapeutic properties in specific breast cancer subtypes is currently lacking. In this study, we characterize these drugs in luminal, endocrine-resistant (MDA-MB-361) and basal-A, triple-negative (MDA-MB-468) breast cancer cells and compare them with previously published data in other breast cancer cell models. Both SKI-II and ABC294640 demonstrated greater efficacy in basal-A compared with luminal breast cancer. ABC294640, in particular, induced apoptosis and blocked proliferation both in vitro and in vivo in this triple-negative breast cancer system. Furthermore, Sphk expression promotes survival and endocrine therapy resistance in previously sensitive breast cancer cells. Taken together, these results characterize sphingosine kinase inhibitors across breast cancer cell systems and demonstrate their therapeutic potential as anti-cancer agents. |
| Databáze: | OpenAIRE |
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