The discovery of metabolic and molecular markers that help improving the detection and diagnosis of breast cancer is an important goal to be achieved. A high composite-choline signal in magnetic resonance spectra of breast lesions has been demonstrated to improve the accuracy of breast cancer diagnosis. In the present study we revealed the principal molecular and biochemical steps associated with the induction of choline metabolism and phosphocholine accumulation in human breast cancer cell-lines in comparison with normal human mammary epithelial cells. We found upregulation of the expression levels of specific choline transporters: organic cation transporter-2 and choline high affinity transporter-1, as well as of the enzyme choline kinase alpha in the cancerous cells in comparison with that in the normal mammary epithelial cells. The expression levels of choline transporter like-1, organic cation transporter-1 and choline kinase beta were similar in normal and cancerous cells. We further showed that choline transport rates and choline kinase activity indeed increased by several fold in the cancer cells leading to the elevation of phosphocholine. The results strongly suggest that phosphocholine can serve as a biomarker of breast cancer reflecting upregulation of specific choline transporters and choline kinase genes.
(c) 2007 Wiley-Liss, Inc.