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Choline kinase overexpression increases invasiveness and drug resistance of human breast cancer cells
Author(s) -
Shah Tariq,
Wildes Flonne,
Penet MarieFrance,
Winnard Paul T.,
Glunde Kristine,
Artemov Dmitri,
Ackerstaff Ellen,
Gimi Barjor,
Kakkad Samata,
Raman Venu,
Bhujwalla Zaver M.
Publication year - 2010
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.1510
Subject(s) - phosphocholine , choline kinase , cancer cell , cancer research , biology , choline , chemistry , cancer , medicine , endocrinology , phospholipid , biochemistry , membrane , phosphatidylcholine
A direct correlation exists between increased choline kinase (Chk) expression, and 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 were studied 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.