Jannie P. Wijnen1, 2, Lu Jiang1, Tiffany R. Greenwood1, Maria D. Cao3, Balaji Krishnamachary1, Dennis W.J. Klomp2, Kristine Glunde1
1Johns Hopkins University in vivo Cellular and Molecular Imaging Center,Russell H. Morgan Department, Johns Hopkins University School of Medicine, Baltimore, MD, United States; 2Department of Radiology, University Medical Centre Utrecht, Utrecht, Netherlands; 3Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trontheim, Norway
In the present study, we stably silenced glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) using short hairpin RNA (shRNA) against GDPD5 and investigated the effects of this stable GDPD5 silencing in a breast tumour xenograft model with 31P Magnetic Resonance Spectroscopy (MRS). Stable silencing of the GDPD5 gene caused an increase in glycerophosphocholine (GPC) and a decrease in free choline in the tumour. This can be explained by the reduction GDPD5 expression in the GDPD5-silenced tumours, which leads to less degradation of GPC into free choline and glycerol-3-phosphate as GDPD5 confers GPC-PDE activity. We also observed an increase in phosphoethanolamine, which could be caused by phosphorylation of ethanolamine by choline and/or ethanolamine kinase as a compensatory mechanism to maintain high levels of phosphomonoesters in the cells.