Control of Metastasis-Associated Gene Expression by Cell-Surface Beta-1, 6 Branched Oligosaccharide Expression.

摘要

Metastatic breast cancer cells express cell-surface Beta-1,6 branched oligosaccharide structures, which are reduced/absent in normal breast tissue. The biosynthesis at these structures is initiated by the Golgi-localized glycosyltransferase N-Acetylglucosamlnyl- transferase V (GlcNAc-T V). The altered expression or GlcNAc-T V in animal mammary cancer models also influences metastasis. Furthermore, altered transcription of metastasis- associated genes has also been observed in cells with a reduced expression at cell-surface Beta- l,6 branched oligosaccharide expression. The aim at this project is to characterize the altered expression of mRNA in mouse and human mammary cancer- derived cell lines as a function at altered Beta-l,6 branched oligosaccharide expression. This will be accomplished by using DNA Microarray technology to assess the mRNA levels in cell lines transfected with GlcNAc-T V expression vectors. After identification of mRNA molecules that are altered by changes (elevation or reduction) in cell-surface Beta-l,6 branched oligosaccharide expression, the kinetics at induction will be characterized using cell lines with GlcNAc-T V under the control at an inducible promoter.