MUC1 isoform specific monoclonal antibody 6E6/2 detects preferential expression of the novel MUC1/Y protein in breast and ovarian cancer
✍ Scribed by Mor-li Hartman; Amos Baruch; Ilan Ron; Yair Aderet; Merav Yoeli; Orit Sagi-Assif; Shuli Greenstein; Yona Stadler; Mordechai Weiss; Ella Harness; Margalit Yaakubovits; Iafa Keydar; Nechama I. Smorodinsky; Daniel H. Wreschner
- Book ID
- 102649578
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- French
- Weight
- 723 KB
- Volume
- 82
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
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-repeatarray-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.