title: A monoclonal antibody against the oncogenic mucin 1 cytoplasmic domain.
abstract: Mucin 1 (MUC1) is a heterodimeric protein that is aberrantly overexpressed in diverse human carcinomas and certain hematologic malignancies. The transmembrane MUC1-C subunit confers tumorigenicity and is a target for anti-cancer drug development. In this regard, the MUC1-C cytoplasmic domain interacts with multiple effectors that have been linked to transformation. Here we report on the generation of a mouse monoclonal antibody (MAb) against the human MUC1-C cytoplasmic domain (MUC1-CD). This IgG1 MAb, designated anti-MUC1-CD, reacts with the NYGQLDIFP epitope. We show that anti-MUC1-CD is useful in immunoblotting and immunoprecipitation experiments. In addition, anti-MUC1-CD can be used to detect expression of the MUC1-C subunit in formalin-fixed, paraffin-embedded tissues. The MUC1-C inhibitor has entered Phase I evaluation for patients with refractory solid tumors. The present results indicate that the anti-MUC1-CD antibody could be useful as a biomarker to identify patients with tumors that may be responsive to MUC1-C inhibitors.
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Govind
authors.initials: G
authors.lastname: Panchamoorthy
authors.forename: Hala
authors.initials: H
authors.lastname: Rehan
authors.forename: Akriti
authors.initials: A
authors.lastname: Kharbanda
authors.forename: Rehan
authors.initials: R
authors.lastname: Ahmad
authors.forename: Donald
authors.initials: D
authors.lastname: Kufe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D014408:Biomarkers, Tumor / Q000276:immunology; D045744:Cell Line, Tumor; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007114:Immunization; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D007544:Isopropyl Thiogalactoside / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000235:genetics / Q000276:immunology*; D017434:Protein Structure, Tertiary; D013270:Stomach / Q000276:immunology; D016707:Tissue Fixation / Q000379:methods
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; D000939:Epitopes; D007074:Immunoglobulin G; C060192:MUC1 protein, human; D018396:Mucin-1; D007544:Isopropyl Thiogalactoside