Post-translational and transcriptional regulation of glycolipid glycosyltransferase genes in apoptotic breast carcinoma cells: VII. Studied by DNA-microarray after treatment with l-PPMP

Rui Ma, N. Matthew Decker, Vesta Anilus, Joseph R. Moskal, Joseph Burgdorf, James R. Johnson, Manju Basu, Sipra Banerjee, Subhash Basu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Functions of glycosphingolipids on the eukaryotic cell membranes during the onset of oncogenic processes and cell death are not well understood. Inhibitors of glycosphingolipid biosynthesis were recently found to trigger apoptosis in many carcinoma including breast cancer SKBR-3, MCF-7, and MDA-468 cells through either intrinsic or extrinsic apoptotic pathways as we previously reported. These anti-cancer inhibitors could increase ceramide concentration by blocking functions of glycolipid glycosyltransferases (GLTs). In this study, using a novel fluorescent dye (ASK-0) revealed the damage of cell organelle membranes by an inhibitor of glucosylceramide biosynthesis (L-PPMP). A highly drug- and cell-dependent regulation of MAPKs was also found by cis-platin and L-PPMP when inducing apoptosis in SKBR-3, MCF-7, and MDA-468 cells. A dose and time-dependent regulation of GLTs were investigated by enzymatic assay and DNA microarray analyses. These GLTs are involved in biosynthesis of LeX and sialosyl-LeX (neolactosyl-ceramide series) such as GalT-4 (UDP-Gal: LcOse3cer β-galactosyltransferase, GalT-5 (UDP-Gal: nLcOse4Cer α1, 3galactosyltransferase, FucT-3 (GDP-Fucose: LM1 α1, 4fucosyltransferase). A similar effect was observed with the GLTs involved in the biosyntheses of Gg-series gangliosides, such as SAT-4 (CMP-NeuAc: GgOse4Cer α2, 3sialyltransferase, and SAT-2 (CMP-NeuAc: GM3 α2, 8sialyltransferase). The glycol-related gene DNA-microarrays also suggested the transcriptional regulation of several GLTs involved in the biosynthesis of neolactosylceramide containing cell-surface antigens in these apoptotic breast carcinoma cells. In the early apoptotic stages (2 to 6 h after L-PPMP treatment) in addition to GlcT-1 gene, several genes (βGalTs and βGlcNAcTs) in the SA-Lea pathway were stimulated.

Original languageEnglish (US)
Pages (from-to)647-661
Number of pages15
JournalGlycoconjugate Journal
Volume26
Issue number6 SPEC. ISS.
DOIs
StatePublished - Aug 1 2009

Keywords

  • AKS-0
  • Apoptosis
  • Breast carcinoma cells
  • Carpases
  • Cis-platin
  • D-PDMP
  • DNA-microarray
  • FucT
  • GD1b
  • GD3
  • GSL
  • Gangliosides
  • GlcT
  • Glycosyltransferases
  • L-PPMP
  • LM1
  • Le
  • MAPKinases
  • PSS-380
  • Phosphatidylserine
  • SA-Le
  • SA-Le

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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