MUC1 isoform specific monoclonal antibody 6E6/2 detects preferential expression of the novel MUC1/Y protein in breast and ovarian cancer

Int J Cancer. 1999 Jul 19;82(2):256-67. doi: 10.1002/(sici)1097-0215(19990719)82:2<256::aid-ijc17>;2-c.


The products of the MUC1 gene are known to be highly expressed in human breast cancer cells. The best characterized MUC1 protein is a polymorphic, type 1 transmembrane molecule containing a large extracellular domain composed primarily of a variable number of 20 amino acid tandem repeats. We have recently identified a novel protein product of the MUC1 gene, the MUC1/Y protein, that is also a transmembrane protein but is devoid of the tandem repeat array and its immediate flanking sequences. To analyze its expression in tumor cells we generated monoclonal antibodies directed against the MUC1/Y extracellular domain (anti-MUC1/Yex MAbs). Epitope mapping identified the MAb, 6E6, which recognized the MUC1/Y isoform with exquisite specificity- the repeat-array-containing MUC1 isoform could not compete out this immunoreactivity. A 30mer peptide which is unique for MUC1/Y and corresponds to the "join" region generated by the MUC1/Y specific splice, abrogated all 6E6 MAb immunoreactivity towards MUC1/Y. Immunoprecipitation of the MUC1/Y protein with 6E6 MAbs revealed that, in contrast with the proteolytic cleavage of the tandem-repeat-array-containing MUC1 isoform, MUC1/Y is not cleaved. Flow cytometry analyses using the 6E6 MAbs demonstrated that the MUC1/Y isoform is expressed on the cell surface of both MCF-7 breast cancer cells and malignant epithelial cells present in effusions obtained from breast and ovarian cancer patients. Our results unequivocally establish that the MUC1/Y protein is expressed on the surface of breast cancer cells and cells of other epithelial malignancies. The anti-MUC1/Y MAbs described here can target MUC1/Y expressing tumor cells in vivo and are likely to be important reagents both for epithelial tumor diagnosis and immunotherapy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Antibodies, Monoclonal / immunology*
  • Ascites / immunology
  • Ascites / pathology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • DNA, Complementary / genetics
  • Epithelial Cells / metabolism
  • Epitopes / immunology
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mucin-1 / biosynthesis*
  • Mucin-1 / chemistry
  • Mucin-1 / genetics
  • Mucin-1 / immunology
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Pleural Effusion, Malignant / immunology
  • Pleural Effusion, Malignant / pathology
  • Protein Isoforms / biosynthesis*
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / immunology
  • Protein Structure, Secondary
  • RNA Splicing
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics
  • Recombinant Fusion Proteins / immunology
  • Transfection
  • Tumor Cells, Cultured


  • Antibodies, Monoclonal
  • DNA, Complementary
  • Epitopes
  • Mucin-1
  • Neoplasm Proteins
  • Protein Isoforms
  • RNA, Messenger
  • RNA, Neoplasm
  • Recombinant Fusion Proteins