A human monoclonal autoantibody to breast cancer identifies the PDZ domain containing protein GIPC1 as a novel breast cancer-associated antigen Journal Article
| Authors: | Rudchenko, S.; Scanlan, M.; Kalantarov, G.; Yavelsky, V.; Levy, C.; Estabrook, A.; Old, L.; Chan, G. L.; Lobel, L.; Trakht, I. |
| Article Title: | A human monoclonal autoantibody to breast cancer identifies the PDZ domain containing protein GIPC1 as a novel breast cancer-associated antigen |
| Abstract: | Background: We have been studying the native autoimmune response to cancer through the isolation of human monoclonal antibodies that are cancer specific from cancer patients. To facilitate this work we previously developed a fusion partner cell line for human lymphocytes, MFP-2, that fuses efficiently with both human lymph node lymphocytes and peripheral blood lymphocytes. Using this unique trioma fusion partner cell line we isolated a panel of autologous human monoclonal antibodies, from both peripheral blood and lymph node lymphocytes, which are representative of the native repertoire of anti-cancer specific antibodies from breast cancer patients. Methods: The current study employs immunocytochemistry, immunohistochemistry, Western blot analysis as well as Northern blots, Scatchard binding studies and finally SEREX analysis for target antigen identification. Results: By application of an expression cloning technique known as SEREX, we determined that the target antigen for two monoclonal antibodies, 27.B1 and 27.F7, derived from lymph node B-cells of a breast cancer patient, is the PDZ domain-containing protein known as GIPC1. This protein is highly expressed not only in cultured human breast cancer cells, but also in primary and metastatic tumor tissues and its overexpression appears to be cancer cell specific. Confocal microscopy revealed cell membrane and cytoplasmic localization of the target protein, which is consistent with previous studies of this protein. Conclusion: We have determined that GIPC1 is a novel breast cancer-associated immunogenic antigen that is overexpressed in breast cancer. Its role, however, in the initiation and/or progression of breast cancer remains unclear and needs further clarification. © 2008 Rudchenko et al; licensee BioMed Central Ltd. |
| Keywords: | immunohistochemistry; controlled study; human tissue; protein expression; primary tumor; human cell; methodology; protein domain; protein localization; protein analysis; metabolism; metastasis; breast cancer; confocal microscopy; protein targeting; analytic method; cancer cell culture; cell line, tumor; breast neoplasms; tumor antigen; b lymphocyte; monoclonal antibody; gene expression regulation; molecular cloning; gene expression regulation, neoplastic; biosynthesis; antibodies, monoclonal; chemistry; kinetics; antigens, neoplasm; immunocytochemistry; antigen detection; breast tumor; tumor cell line; western blotting; cell membrane; adaptor proteins, signal transducing; autoimmunity; protein structure, tertiary; autoantibody; breast carcinogenesis; signal transducing adaptor protein; autoantibodies; protein tertiary structure; cytosol; human monoclonal antibody; scatchard plot; pdz protein; protein gipc1; gipc1 protein, human; lymph node cell |
| Journal Title: | BMC Cancer |
| Volume: | 8 |
| ISSN: | 1471-2407 |
| Publisher: | Biomed Central Ltd |
| Date Published: | 2008-08-24 |
| Start Page: | 248 |
| Language: | English |
| DOI: | 10.1186/1471-2407-8-248 |
| PUBMED: | 18721486 |
| PROVIDER: | scopus |
| PMCID: | PMC2529336 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 7" - "Export Date: 17 November 2011" - "CODEN: BCMAC" - "Source: Scopus" |
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