Figure 1

Differences in the level of expression of genes for sphingolipid biosynthesis through sulfatides, ST, and the amounts of ST in epithelial ovarian tumors versus normal ovarian stromal tissues. (A) The relative levels of mRNA for the enzymes of the shown steps of the de novo sphingolipid biosynthesis pathway were imported into a KEGG style pathway heatmap [15] with fold differences in gene expression for ovarian cancer/normal stromal cells are represented by the color scale (red = higher; blue = lower). In this depiction, the pathway begins in the upper left corner with the condensation of serine and palmitoyl-CoA by serine palmitoyltransferase (SPT, shown for its three known genes) to form 3-ketosphinganine (3KSa) which is converted to sphinganine (Sa) by 3KSa reductase. Sa is N-acylated to dihydroceramide (DHCer) by a family of Cer synthases (CerS), desaturated (by DHCer desaturases, DES), and converted to sphingomyelin (SM) by SM synthases (SMS), phosphorylated to Cer 1-phosphate by Cer kinase (CERK) (this branch of sphingolipid biosynthesis is also thought to involve a Cer transport protein, CERT), or glycosylated to glucosylceramide (GlcCer) or galactosylceramide (GalCer), which can undergo sulfation to ST by GalCer sulfotransferase (Gal3ST1). Also shown are the steps of ST turnover, via aryl sulfatase (ARSA) and galactocerebrosidase (GALC) which operate in concert with prosaposins (PSAP), and GlcCer turnover via glucosylcerebrosidase (GBA1). The heat maps depict the normalized level of expression of these genes in the epithelial ovarian tumors divided by the level of expression on normal stromal tissues averaged for the 12 patients and 8 controls. (B and C) Amounts of the various N-acyl-chain length subspecies of ST as measured by LC ESI-MS/MS for clinically similar patients with ovarian carcinoma (B, n = 12) or normal ovary (C, n = 12).