Activation of phosphatidylcholine cycle enzymes in human epithelial ovarian cancer cells

Cancer Res. 2010 Mar 1;70(5):2126-35. doi: 10.1158/0008-5472.CAN-09-3833. Epub 2010 Feb 23.


Altered phosphatidylcholine (PC) metabolism in epithelial ovarian cancer (EOC) could provide choline-based imaging approaches as powerful tools to improve diagnosis and identify new therapeutic targets. The increase in the major choline-containing metabolite phosphocholine (PCho) in EOC compared with normal and nontumoral immortalized counterparts (EONT) may derive from (a) enhanced choline transport and choline kinase (ChoK)-mediated phosphorylation, (b) increased PC-specific phospholipase C (PC-plc) activity, and (c) increased intracellular choline production by PC deacylation plus glycerophosphocholine-phosphodiesterase (GPC-pd) or by phospholipase D (pld)-mediated PC catabolism followed by choline phosphorylation. Biochemical, protein, and mRNA expression analyses showed that the most relevant changes in EOC cells were (a) 12-fold to 25-fold ChoK activation, consistent with higher protein content and increased ChoKalpha (but not ChoKbeta) mRNA expression levels; and (b) 5-fold to 17-fold PC-plc activation, consistent with higher, previously reported, protein expression. PC-plc inhibition by tricyclodecan-9-yl-potassium xanthate (D609) in OVCAR3 and SKOV3 cancer cells induced a 30% to 40% reduction of PCho content and blocked cell proliferation. More limited and variable sources of PCho could derive, in some EOC cells, from 2-fold to 4-fold activation of pld or GPC-pd. Phospholipase A2 activity and isoform expression levels were lower or unchanged in EOC compared with EONT cells. Increased ChoKalpha mRNA, as well as ChoK and PC-plc protein expression, were also detected in surgical specimens isolated from patients with EOC. Overall, we showed that the elevated PCho pool detected in EOC cells primarily resulted from upregulation/activation of ChoK and PC-plc involved in PC biosynthesis and degradation, respectively.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Choline Kinase / biosynthesis
  • Choline Kinase / genetics
  • Choline Kinase / metabolism
  • Enzyme Activation
  • Epithelial Cells / pathology
  • Female
  • Humans
  • Membrane Transport Proteins / biosynthesis
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Ovarian Neoplasms / enzymology*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Phosphatidylcholines / biosynthesis*
  • Phospholipase D / metabolism
  • Phosphoric Diester Hydrolases / metabolism
  • Type C Phospholipases / metabolism


  • Membrane Transport Proteins
  • Phosphatidylcholines
  • choline transporter
  • Choline Kinase
  • Phosphoric Diester Hydrolases
  • Type C Phospholipases
  • glycerophosphocholine phosphodiesterase
  • phosphatidylcholine-specific phospholipase C
  • Phospholipase D