title: A 17-kDa CD4-binding glycoprotein present in human seminal plasma and in breast tumor cells.
abstract: We previously isolated gp17, a human seminal plasma glycoprotein, which specifically interacts with the D1-D2 region of CD4, a T cell surface molecule involved in antigen recognition mediated by helper T cells also acting as a receptor for the human immunodeficiency virus. In this study we report that monoclonal antibodies (mAb) reacting with gp17 are able to inhibit the binding of gp17 to immobilized soluble CD4. An immunohistochemical analysis shows that gp17 is also expressed in mammary tumor cells upon hormone treatment and in biopsies from breast cancer patients. A structural characterization of gp17, including amino acid sequencing, indicates that the protein has an extensive structural similarity with a glycoprotein designated as seminal actin-binding protein (SABP), also secreted by male sexual glands. SABP is in turn identical to gross cystic disease fluid protein-15 (GCDFP-15) or prolactin-inducible protein (PIP), a factor known as a highly specific and sensitive marker of primary and metastatic apocrine breast cancer. To establish further the correspondence of gp17 and GCDFP-15/PIP/SABP, the latter was expressed in bacteria from a cloned cDNA and purified by affinity chromatography to either anti-gp17 mAb-Sepharose or CD4-Sepharose. The purified recombinant protein is shown to inhibit the binding of labeled, pure g17 to immobilized soluble CD4. The finding that breast cancer cells express a protein able to interact with the CD4 domains involved in the recognition of class II major histocompatibility antigens suggests a possible mechanism by which a tumor may affect the activity of tumor-infiltrated CD4+ T cells.
authors.affiliation: International Institute of Genetics and Biophysics, CNR, Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Autiero
authors.forename: G
authors.initials: G
authors.lastname: Cammarota
authors.forename: A
authors.initials: A
authors.lastname: Friedlein
authors.forename: M
authors.initials: M
authors.lastname: Zulauf
authors.forename: G
authors.initials: G
authors.lastname: Chiappetta
authors.forename: V
authors.initials: V
authors.lastname: Dragone
authors.forename: J
authors.initials: J
authors.lastname: Guardiola
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001053:Apolipoproteins; D053399:Apolipoproteins D; D001483:Base Sequence; D001943:Breast Neoplasms / Q000737:chemistry*; D015704:CD4 Antigens / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry*; D002352:Carrier Proteins / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification* / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D006023:Glycoproteins / Q000276:immunology / Q000302:isolation & purification* / Q000378:metabolism; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000276:immunology / Q000302:isolation & purification* / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012661:Semen / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
chemical_list: C024328:APOD protein, human; D000911:Antibodies, Monoclonal; D001053:Apolipoproteins; D053399:Apolipoproteins D; D015704:CD4 Antigens; D002352:Carrier Proteins; D018076:DNA, Complementary; D006023:Glycoproteins; D026901:Membrane Transport Proteins; D009363:Neoplasm Proteins; C488892:PIP protein, human; D010446:Peptide Fragments; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins