Down regulation of HIF-1 alpha in MDA-MB-231 Human Breast Cancer Cells Alters Choline Phospholipid Metabolism

Introduction: Hypoxia-inducible factor-1 (HIF-1) is a heterodimer made up of an oxygen-regulated HIF-1α subunit and a constitutively expressed HIF-1β subunit. Under hypoxic conditions, HIF-1α is stabilized and binds to hypoxia response elements that act as transcriptional controls of several genes. Among the 70 target genes of HIF-1 known so far, several are involved in angiogenesis, cell proliferation, cell viability, and glucose and iron metabolisms. HIF-1α over-expression has been associated with an increased patient mortality rate in many cancer types including breast cancer [1]. Suppression of HIF-1α gene expression has been shown to be sufficient in tumor growth repression [2]. Here we have studied the effect of HIF-1α silencing on the metabolism of MDA-MB-231 cells using an MR compatible cell perfusion assay. We found that HIF-1α silenced cells exhibited significantly reduced choline kinase (Chk) expression together with reduced total choline (tCho), and phosphocholine (PC) compared to parental cells.