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MUC1 isoform specific monoclonal antibody 6E6/2 detects preferential expression of the novel MUC1/Y protein in breast and ovarian cancer
Author(s) -
Hartman Morli,
Baruch Amos,
Ron Ilan,
Aderet Yair,
Yoeli Merav,
SagiAssif Orit,
Greenstein Shuli,
Stadler Yona,
Weiss Mordechai,
Harness Ella,
Yaakubovits Margalit,
Keydar Iafa,
Smorodinsky Nechama I.,
Wreschner Daniel H.
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990719)82:2<256::aid-ijc17>3.0.co;2-c
Subject(s) - muc1 , gene isoform , monoclonal antibody , biology , microbiology and biotechnology , immunoprecipitation , tandem repeat , epitope , transmembrane protein , antigen , cancer research , antibody , gene , biochemistry , receptor , genetics , genome
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. Int. J. Cancer 82:256–267, 1999. © 1999 Wiley‐Liss, Inc.