The calcium pump plasma membrane Ca(2+)-ATPase 2 (PMCA2) regulates breast cancer cell proliferation and sensitivity to doxorubicin
| Autor: | Gregory R. Monteith, Michael J. G. Milevskiy, Sarah J. Roberts-Thomson, Sunil R. Lakhani, Merril C. Curry, Lynne Reid, Melissa A. Brown, Leonard Da Silva, Jodi M. Saunus, Eloise Dray, Chanel E. Smart, Amelia A. Peters, Daneth L. Marcial, Wei C. Lee |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Calcium pump Breast Neoplasms Biology Article 03 medical and health sciences Plasma Membrane Calcium-Transporting ATPases Breast cancer Internal medicine Cell Line Tumor medicine Gene silencing Humans Lactation Doxorubicin Calcium Signaling RNA Messenger RNA Small Interfering Mammary Glands Human Cell Proliferation Calcium metabolism Multidisciplinary Antibiotics Antineoplastic Cell growth Cell Membrane Epithelial Cells medicine.disease Survival Analysis Gene Expression Regulation Neoplastic Isoenzymes 030104 developmental biology Endocrinology Cell Transformation Neoplastic Hormone receptor Apoptosis Carcinoma Basal Cell Cancer research Calcium Female sense organs medicine.drug |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Regulation of Ca2+ transport is vital in physiological processes, including lactation, proliferation and apoptosis. The plasmalemmal Ca2+ pump isoform 2 (PMCA2) a calcium ion efflux pump, was the first protein identified to be crucial in the transport of Ca2+ ions into milk during lactation in mice. In these studies we show that PMCA2 is also expressed in human epithelia undergoing lactational remodeling and also report strong PMCA2 staining on apical membranes of luminal epithelia in approximately 9% of human breast cancers we assessed. Membrane protein expression was not significantly associated with grade or hormone receptor status. However, PMCA2 mRNA levels were enriched in Basal breast cancers where it was positively correlated with survival. Silencing of PMCA2 reduced MDA-MB-231 breast cancer cell proliferation, whereas silencing of the related isoforms PMCA1 and PMCA4 had no effect. PMCA2 silencing also sensitized MDA-MB-231 cells to the cytotoxic agent doxorubicin. Targeting PMCA2 alone or in combination with cytotoxic therapy may be worthy of investigation as a therapeutic strategy in breast cancer. PMCA2 mRNA levels are also a potential tool in identifying poor responders to therapy in women with Basal breast cancer. |
| Databáze: | OpenAIRE |
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