Proceedings of the National Academy of Sciences - PNAS, 2012-10, Vol.109 (40), p.16282-16287
2012
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Transient receptor potential channel TRPC5 is essential for P-glycoprotein induction in drug-resistant cancer cells
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2012-10, Vol.109 (40), p.16282-16287
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2012
- Quelle
- Elektronische Zeitschriftenbibliothek
- Beschreibungen/Notizen
- An attractive strategy to overcome multidrug resistance in cancer chemotherapy is to suppress P-glycoprotein (P-gp), which is a pump overproduced in cancer cells to remove cytotoxic drugs from cells. In the present study, a Ca ²⁺-permeable channel TRPC5 was found to be overproduced together with P-gp in adriamycin-resistant breast cancer cell line MCF-7/ADM. Suppressing TRPC5 activity/expression reduced the P-gp induction and caused a remarkable reversal of adriamycin resistance in MCF-7/ADM. In an athymic nude mouse model of adriamycin-resistant human breast tumor, suppressing TRPC5 decreased the growth of tumor xenografts. Nuclear factor of activated T cells isoform c3 (NFATc3) was the transcriptional factor that links the TRPC5 activity to P-gp production. Together, we demonstrated an essential role of TRPC5–NFATc3–P-gp signaling cascade in P-gp induction in drug-resistant cancer cells.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.1202989109Titel-ID: cdi_pnas_primary_109_40_16282
- Format
- –
- Schlagworte
- animal models, Animals, ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism, B lymphocytes, Biological Sciences, breast neoplasms, Breast Neoplasms - drug therapy, Breast Neoplasms - metabolism, calcium, Cell lines, cytotoxicity, Doxorubicin, Drug Resistance, Multiple - physiology, drug therapy, Female, Gene Expression Regulation, Neoplastic - physiology, Genes, HEK293 cells, Heterologous transplantation, Humans, Luciferases, MCF-7 Cells, Mice, Mice, Nude, Multiple drug resistance, neoplasm cells, NFATC Transcription Factors - metabolism, Patch-Clamp Techniques, Signal Transduction - physiology, Small interfering RNA, T lymphocytes, transcription factors, transient receptor potential channels, TRPC Cation Channels - metabolism, Tumor cell line, Tumors