Choline kinase overexpression increases invasiveness and drug resistance of human breast cancer cells Journal Article
| Authors: | Shah, T.; Wildes, F.; Penet, M. F.; Winnard, P. T. Jr; Glunde, K.; Artemov, D.; Ackerstaff, E.; Gimi, B.; Kakkad, S.; Raman, V.; Bhujwalla, Z. M. |
| Article Title: | Choline kinase overexpression increases invasiveness and drug resistance of human breast cancer cells |
| Abstract: | A direct correlation exists between increased choline kinase (Chk) expression, the resulting increase of phosphocholine levels, and histological tumor grade. To better understand the function of Chk and choline phospholipid metabolism in breast cancer we have stably overexpressed one of the two isoforms of Chk-α, known to be upregulated in malignant cells, in non-invasive MCF-7 human breast cancer cells. Dynamic tracking of cell invasion and cell metabolism was perfomed with a magnetic resonance (MR) compatible cell perfusion assay. The MR based invasion assay demonstrated that MCF-7 cells overexpressing Chk-α (MCF-7-Chk) exhibited an increase of invasion relative to control MCF-7 cells (0.84 vs 0.3). Proton MR spectroscopy studies showed significantly higher phosphocholine and elevated triglyceride signals in Chk overexpressing clones compared to control cells. A test of drug resistance in MCF-7-Chk cells revealed that these cells had an increased resistance to 5-fluorouracil and higher expression of thymidylate synthase compared to control MCF-7 cells. To further characterize increased drug resistance in these cells, we performed rhodamine-123 efflux studies to evaluate drug efflux pumps. MCF-7-Chk cells effluxed twice as much rhodamine-123 compared to MCF-7 cells. Chk-α overexpression resulted in MCF-7 human breast cancer cells acquiring an increasingly aggressive phenotype, supporting the role of Chk-α in mediating invasion and drug resistance, and the use of phosphocholine as a biomarker of aggressive breast cancers. Copyright © 2010 John Wiley & Sons, Ltd. |
| Keywords: | controlled study; protein expression; unclassified drug; human cell; fluorouracil; nuclear magnetic resonance imaging; phenotype; cytology; metabolism; breast cancer; tumor markers, biological; drug resistance; drug resistance, neoplasm; cell line, tumor; breast neoplasms; extracellular matrix; cancer cell; isoforms; magnetic resonance; magnetic resonance spectroscopy; triacylglycerol; upregulation; magnetic materials; thymidylate synthase; 5-fluorouracil; cell metabolism; cell invasion; invasion; clone cells; choline kinase; choline kinase alpha; mcf-7 cells; organisms, genetically modified; isoenzymes; over-expression; phospholipids; phosphorylcholine; phospholipid; human breast cancer cells; non-invasive; choline phospholipid metabolism; control-cell; drug efflux pumps; dynamic tracking; invasiveness; malignant cells; phosphocholine; proton mr spectroscopy; tumor grades; particle detectors; rhodamine 123; phospholipid metabolism |
| Journal Title: | NMR in Biomedicine |
| Volume: | 23 |
| Issue: | 6 |
| ISSN: | 0952-3480 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2010-07-01 |
| Start Page: | 633 |
| End Page: | 642 |
| Language: | English |
| DOI: | 10.1002/nbm.1510 |
| PUBMED: | 20623626 |
| PROVIDER: | scopus |
| PMCID: | PMC3115627 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "CODEN: NMRBE" - "Source: Scopus" |
