RNA interference-mediated choline kinase suppression in breast cancer cells induces differentiation and reduces proliferation.
Article Details
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Glunde K, Raman V, Mori N, Bhujwalla ZM
RNA interference-mediated choline kinase suppression in breast cancer cells induces differentiation and reduces proliferation.
Cancer Res. 2005 Dec 1;65(23):11034-43.
- PubMed ID
- 16322253 [ View in PubMed]
- Abstract
Choline kinase is overexpressed in breast cancer cells and activated by oncogenes and mitogenic signals, making it a potential target for cancer therapy. Here, we have examined, for the first time, the effects of RNA interference (RNAi)-mediated down-regulation of choline kinase in nonmalignant and malignant human breast epithelial cell lines using magnetic resonance spectroscopy (MRS) as well as molecular analyses of proliferation and differentiation markers. RNAi knockdown of choline kinase reduced proliferation, as detected by proliferating cell nuclear antigen and Ki-67 expression, and promoted differentiation, as detected by cytosolic lipid droplet formation and expression of galectin-3. The functional importance of RNAi-mediated choline kinase down-regulation on choline phospholipid metabolism was confirmed by the significant reduction of phosphocholine detected by MRS. These results strongly support the targeting of choline kinase in breast cancer cells with RNAi and show the potential ability of noninvasive MRS to detect and evaluate future treatments incorporating such strategies.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Choline Choline kinase alpha Protein Humans UnknownSubstrateDetails Choline salicylate Choline kinase alpha Protein Humans UnknownSubstrateDetails