ArticleBreast cancer research : BCR2010
17-allyamino-17-demethoxygeldanamycin treatment results in a magnetic resonance spectroscopy-detectable elevation in choline-containing metabolites associated with increased expression of choline transporter SLC44A1 and phospholipase A2.
Article in Breast cancer research : BCR, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 31 citations in OpenAlex.
- Cellular Lactate Spectroscopy Using 1.5 Tesla Clinical Apparatus.International journal of molecular sciences · 2022Article
- A novel roadmap connecting theEuropean radiology experimental · 2021Review
- Choline transport for phospholipid synthesis: An emerging role of choline transporter-like protein 1.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- Choline kinase alpha-Putting the ChoK-hold on tumor metabolism.Progress in lipid research · 2016Review
- CEST-MRI detects metabolite levels altered by breast cancer cell aggressiveness and chemotherapy response.NMR in biomedicine · 2016Article
- Changes in pyruvate metabolism detected by magnetic resonance imaging are linked to DNA damage and serve as a sensor of temozolomide response in glioblastoma cells.Cancer research · 2014Article
- Metabolic Effects of Known and Novel HDAC and SIRT Inhibitors in Glioblastomas Independently or Combined with Temozolomide.Metabolites · 2014Article
- Hyperpolarized [1-13C] glutamate: a metabolic imaging biomarker of IDH1 mutational status in glioma.Cancer research · 2014Article
- Silencing of the glycerophosphocholine phosphodiesterase GDPD5 alters the phospholipid metabolite profile in a breast cancer model in vivo as monitored by (31) P MRS.NMR in biomedicine · 2014Article
- MR-detectable metabolic consequences of mitogen-activated protein kinase kinase (MEK) inhibition.NMR in biomedicine · 2014Article
- Lactate dehydrogenase A silencing in IDH mutant gliomas.Neuro-oncology · 2014Article
- Treatment with the MEK inhibitor U0126 induces decreased hyperpolarized pyruvate to lactate conversion in breast, but not prostate, cancer cells.NMR in biomedicine · 2013Article
- Non-invasive in vivo assessment of IDH1 mutational status in glioma.Nature communications · 2013Article
- HDAC inhibition induces increased choline uptake and elevated phosphocholine levels in MCF7 breast cancer cells.PloS one · 2013Article
- 1H NMR metabolomics analysis of glioblastoma subtypes: correlation between metabolomics and gene expression characteristics.The Journal of biological chemistry · 2012Article
- Effects of HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) on NEU/HER2 overexpressing mammary tumours in MMTV-NEU-NT mice monitored by Magnetic Resonance Spectroscopy.BMC research notes · 2012Article
- Reduced phosphocholine and hyperpolarized lactate provide magnetic resonance biomarkers of PI3K/Akt/mTOR inhibition in glioblastoma.Neuro-oncology · 2012Article
- Metabolic consequences of treatment with AKT inhibitor perifosine in breast cancer cells.NMR in biomedicine · 2012Article
- Choline metabolism in malignant transformation.Nature reviews. Cancer · 2011Review
- Metabolic effects of signal transduction inhibition in cancer assessed by magnetic resonance spectroscopy.Molecular oncology · 2011Review
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3 authors at 1 institution in 1 country.
Funding
Abstract
introduction17-allyamino-17-demethoxygeldanamycin (17-AAG), a small molecule inhibitor of Hsp90, is currently in clinical trials in breast cancer. However, 17-AAG treatment often results in inhibition of tumor growth rather than shrinkage, making detection of response a challenge. Magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) are noninvasive imaging methods than can be used to monitor metabolic biomarkers of drug-target modulation. This study set out to examine the MRS-detectable metabolic consequences of Hsp90 inhibition in a breast cancer model.
methodsMCF-7 breast cancer cells were investigated, and MRS studies were performed both on live cells and on cell extracts. (31)P and (1)H MRS were used to determine total cellular metabolite concentrations and (13)C MRS was used to probe the metabolism of [1,2-(13)C]-choline. To explain the MRS metabolic findings, microarray and RT-PCR were used to analyze gene expression, and in vitro activity assays were performed to determine changes in enzymatic activity following 17-AAG treatment.
resultsTreatment of MCF-7 cells with 17-AAG for 48 hours caused a significant increase in intracellular levels of choline (to 266 ± 18% of control, P = 0.05) and phosphocholine (PC; to 181 ± 10% of control, P = 0.001) associated with an increase in expression of choline transporter SLC44A1 and an elevation in the de novo synthesis of PC. We also detected an increase in intracellular levels of glycerophosphocholine (GPC; to 176 ± 38% of control, P = 0.03) associated with an increase in PLA2 expression and activity.
conclusionsThis study determined that in the MCF-7 breast cancer model inhibition of Hsp90 by 17-AAG results in a significant MRS-detectable increase in choline, PC and GPC, which is likely due to an increase in choline transport into the cell and phospholipase activation. (1)H MRSI can be used in the clinical setting to detect levels of total choline-containing metabolite (t-Cho, composed of intracellular choline, PC and GPC). As Hsp90 inhibitors enter routine clinical use, t-Cho could thus provide an easily detectable, noninvasive metabolic biomarker of Hsp90 inhibition in breast cancer patients.
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