Choline kinase overexpression increases invasiveness and drug resistance of human breast cancer cells

Tariq Shah, Flonne Wildes, Marie France Penet, Paul T. Winnard, Kristine Glunde, Dmitri Artemov, Ellen Ackerstaff, Barjor Gimi, Samata Kakkad, Venu Raman, Zaver M. Bhujwalla

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)633-642
Number of pages10
JournalNMR in biomedicine
Volume23
Issue number6
DOIs
StatePublished - Jul 2010

Keywords

  • Choline kinase
  • Drug resistance
  • Invasion
  • MCF-7 cells
  • Magnetic resonance spectroscopy

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Spectroscopy

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