Methyl-3H-Choline Incorporation into MCF-7 Cells: Correlation with Proliferation:Choline Kinase and Phospholipase D Assay

摘要

[Methyl-11C]-choline is a new positron emission tomography (PET) imaging agent, whichwas introduced to image prostate cancer but the identity of metabolites producing the 11C signal intumour cells during [methyl-11C]-choline-PET imaging in prostate cancer patients is still unknown.Many studies demonstrated that choline incorporation is related to cellular proliferation, and rapidlyproliferating cells increase their demands for phospholipids synthesis. Choline kinase (ChoK) enzymeis the first step to phosphorylate choline to form phosphocholine (Pcho) and subsequentlyphosphatidylcholine (PtdCho), the most constituent of cellular phospholipids membranes. There issome evidence that indicates that phospholipase D (PLD) activity is involved in enhancing cellproliferation and transformation. The hydrolysis of PtdCho by PLD leads to the formation of choline.In this study, whether ChoK or PLD level is related to cellular proliferation or not was investigated.The activity of ChoK and PLD were determined in rapidly proliferating and confluent breast cancerMCF-7 cells. The activity of ChoK as well as PLD were significantly higher in the exponentiallygrowing cell populations, resulting in increased phosphocholine (Pcho) production, approximately60% of the aqueous fraction of the cell, in the exponentially growing cells compared to the confluentcells. This study indicates that the major water-soluble choline metabolite was Pcho as a consequenceof increased ChoK and PLD activity in the rapidly proliferating cells compared to the confluent cells.