Expression of sialyl-Tn antigen in breast cancer cells transfected with the human CMP-Neu5Ac: GalNAc alpha2,6-sialyltransferase (ST6GalNac I) cDNA

Glycoconj J. 2001 Nov-Dec;18(11-12):883-93. doi: 10.1023/a:1022200525695.

Abstract

Sialyl-Tn antigen (STn) is a cancer associated carbohydrate antigen over-expressed in several cancers including breast cancer, and currently associated with more aggressive diseases and poor prognosis. However, the commonly used breast cancer cell lines (MDA-MB-231, T47-D and MCF7) do not express STn antigen. The key step in the biosynthesis of STn is the transfer of a sialic acid residue in alpha2,6-linkage to GalNAc alpha-O-Ser/Thr. This reaction is mainly catalyzed by a CMP-Neu5Ac GalNAc alpha2,6-sialyltransferase: ST6GalNAc I. In order to generate STn-positive breast cancer cells, we have cloned a cDNA encoding the full-length human ST6GalNAc I from HT-29-MTX cells. The stable transfection of MDA-MB-231 with an expression vector encoding ST6GalNAc I induces the expression of STn antigen at the cell surface. The expression of STn short cuts the initial O-glycosylation pattern of these cell lines, by competing with the Core-1 beta1,3-galactosyltransferase, the first enzyme involved in the elongation of O-glycan chains. Moreover, we show that STn expression is associated with morphological changes, decreased growth and increased migration of MDA-MB-231 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Tumor-Associated, Carbohydrate / chemistry
  • Antigens, Tumor-Associated, Carbohydrate / metabolism*
  • Biomarkers, Tumor
  • Breast Neoplasms / genetics
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carbohydrate Conformation
  • Carbohydrate Sequence
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Cell Movement
  • Cloning, Molecular
  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / genetics
  • DNA, Complementary / genetics
  • Female
  • Galactosyltransferases / metabolism
  • Glycosylation
  • Humans
  • Molecular Sequence Data
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sialyltransferases / genetics*
  • Sialyltransferases / metabolism
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Antigens, Tumor-Associated, Carbohydrate
  • Biomarkers, Tumor
  • DNA, Complementary
  • Tn antigen
  • sialosyl-Tn antigen
  • Galactosyltransferases
  • glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase
  • Sialyltransferases
  • CMP-N-acetylneuraminate-alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase