Differential Role of Human Choline Kinase α and β Enzymes in Lipid Metabolism: Implications in Cancer Onset and Treatment

• DOI: 10.1371/journal.pone.0007819
• Publication Date: 2009-11-12T00:59:26Z
• Authors: David Gallego-Ortega; Ana Ramirez de Mo...; Maria Angeles Ramos; Fatima Valdes-Mora; Maria Gonzalez Ba...; Jacinto Sarmenter...; Juan Carlos Lacal
• Keywords: Choline kinase; Phosphocholine; Choline

Background The Kennedy pathway generates phosphocoline and phosphoethanolamine through its two branches. Choline Kinase (ChoK) is the first enzyme of branch synthesis phosphocholine, major component plasma membrane. ChoK family proteins composed by ChoKα ChoKβ isoforms, one with different variants splicing. Recently has been implicated in carcinogenic process, since it over-expressed a variety human cancers. However, no evidence for role carcinogenesis reported. Methodology/Principal Findings Here we compare vitro vivo properties ChoKα1 lipid metabolism, their potential carcinogenesis. Both showed choline ethanolamine kinase activities when assayed cell extracts, though affinity substrates. they behave differentially overexpressed whole cells. Whereas display an role, present dual choline/ethanolamine suggesting involvement each isoform distinct biochemical pathways under conditions. In addition, while overexpression oncogenic HEK293T or MDCK cells, not sufficient to induce transformation nor tumor growth. Furthermore, significant upregulation mRNA levels panel breast lung cancer lines was found, but changes were observed. Finally, MN58b, previously described potent inhibitor antitumoral activity, shows more than 20-fold higher efficiency towards ChoKβ. Conclusion/Significance This study represents metabolic physiological roles implications These findings constitute step forward design strategy based on inhibition.