Antiproliferative effect of D-glucuronyl C5-epimerase in human breast cancer cells

D-glucuronyl C5-epimerase expression was significantly decreased in MCF7 cells compared to normal human breast tissue. Re-expression of GLCE inhibited proliferative activity of MCF7 cells according to CyQUANT NF Cell Proliferation Assay, while it did not affect their viability in Colony Formation Test. According to Cancer PathFinder RT Profiler PCR Array, antiproliferative effect of GLCE in vitro could be related to the enhanced expression of tumour suppressor genes р53 (+3.3 fold), E2F1 (+3.00 fold), BRCA1 (+3.5 fold), SYK (+8.1 fold) and apoptosis-related genes BCL2 (+4.2 fold) and NFKB1 (+2.6 fold). Also, GLCE re-expression in MCF7 cells considerably changed the expression of some genes involved in angiogenesis (IL8, +4.6 fold; IFNB1, +3.9 fold; TNF, +4.6 fold and TGFB1, -5.7 fold) and invasion/metastasis (SYK, +8.1 fold; NME1, +3.96 fold; S100A4, -4.6 fold).The ability of D-glucuronyl С5-epimerase to suppress proliferation of breast cancer cells MCF7 through the attenuated expression of different key genes involved in cell cycle regulation, angiogenesis and metastasis molecular pathways supports the idea on the involvement of the gene in regulation of breast cancer cell proliferation.D-glucuronyl C5-epimerase (GLCE) is one of the key enzymes responsible for biosynthesis of the carbohydrate part of heparan sulfate proteoglycans (HSPGs) - complex protein-carbohydrate molecules localized on the cell surface and in extracellular matrix (ECM). HSPGs interact with numerous ligands, including many growth factors, cytokines, receptors and extracellular matrix molecules and mediate cell signaling events controlling migration, proliferation and differentiation [1-4]. Abnormal expression or deregulated function of these proteoglycans crucially affect cell-cell and cell-matrix interactions and promote different pathologies including malignant transformation [5,6].In many cases, the structure of the heparan sulfate (HS) polysaccharide chains is a major determinant of HSPGs f