RNA interference-mediated choline kinase suppression in breast cancer cells induces differentiation and reduces proliferation.
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.
Glunde
Kristine
K
John Hopkins University In Vivo Cellular Molecular Imaging Center Program, Russell H. Morgan Department of Radiology and Radiological Science, John Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Raman
Venu
V
Mori
Noriko
N
Bhujwalla
Zaver M
ZM
D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002794:Choline / Q000378:metabolism; D002797:Choline Kinase / Q000037:antagonists & inhibitors* / Q000235:genetics; D015536:Down-Regulation; D006801:Humans; D008279:Magnetic Resonance Imaging; D010743:Phospholipids / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection
D010743:Phospholipids; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D002797:Choline Kinase; D002794:Choline