Differential antibody reactivity and CD4 binding of the mammary tumor marker protein GCDFP-15 from breast cyst and its counterparts from exocrine epithelia.
Analysis of biopsies from breast cancer patients demonstrated that GCDFP-15 (gross cystic disease fluid protein-15) is a specific immunocytochemical marker of primary and secondary apocrine breast tumors. The protein has an amino acid sequence identical to SABP (secretory actin-binding protein), to PIP (prolactin-inducible protein) and to gp17, a protein isolated from human seminal plasma. The latter was found to bind to CD4, a T-cell co-receptor involved in antigen recognition, thereby inhibiting the ability of the receptor to interact with the HIV-1 envelope protein gp120. We compare here the ability of independently purified GCDFP-15, SABP and gp17 and of recombinant PIP both to cross-react with a panel of monoclonal antibodies (MAbs) raised against GCDFP-15 or gp17, respectively, and to bind to CD4. We show that, although the various factors share the ability to bind to the panel of antibodies used, differences in the pattern of MAb recognition can be demonstrated. By comparing the kinetic constants for binding of GCDFP-5 and gp17 to CD4 by biosensor technology, significant differences in binding affinities were observed between the 2 factors, thus reflecting structural differences. Surface plasmon resonance analysis also showed that anti-GCDFP-15 and anti-gp17 antibodies inhibit the binding of CD4 to GCDFP-15 and gp17, respectively, to different extents. Our data thus indicate that, while the various forms of the protein are encoded by the same cDNA, tissue specificities due to post-translational modifications exist. This information may be relevant for developing more sensitive and accurate tests for the use of GCDFP-15 as a diagnostic mammary tumor marker and, most importantly, raises the possibility that GCDFP-15 may constitute a breast tumor-specific antigen.
International Institute of Genetics and Biophysics, CNR, Naples, Italy. affei@iigbna.iigb.na.cnr.it
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Caputo
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Autiero
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Mani
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Basmaciogullari
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Basmociogullari
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Piatier-Tonneau
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Guardiola
D000911:Antibodies, Monoclonal / Q000378:metabolism; D001053:Apolipoproteins; D053399:Apolipoproteins D; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism*; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005348:Fibrocystic Breast Disease / Q000276:immunology / Q000378:metabolism*; D006023:Glycoproteins; D006801:Humans; D007120:Immunochemistry; D026901:Membrane Transport Proteins; D008840:Microfilament Proteins / Q000276:immunology / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism*
C024328:APOD protein, human; D000911:Antibodies, Monoclonal; D001053:Apolipoproteins; D053399:Apolipoproteins D; D015704:CD4 Antigens; D002352:Carrier Proteins; D006023:Glycoproteins; D026901:Membrane Transport Proteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; C488892:PIP protein, human