title: Anti-centrosome antibodies in breast cancer are the expression of autoimmunity.
abstract: Centrosome abnormalities have been observed in nearly all human solid tumors, but their role in tumorigenesis is unclear. We have demonstrated that autoantibodies reacting with antigens in centrosomes are frequently found in BC sera. In this work, we attempted to characterize the centrosome antigens associated with BC. We immunoscreened a T7 cDNA library of BC proteins with BC sera, and the autoantigens identified were printed as a microarray and hybridized with BC and control sera. We used immunohistochemistry (IHC) to investigate the expression of the cloned autoantigens in BC tissue. Immunoscreening with BC sera led to the cloning of autoantibodies recognizing epitopes developing in a family of proteins located on centrosomes such as peri-centriolar material-1, isomorph CRA, stathmin1, HS actin gamma1, SUMO/sentrin peptidase 2, and ubiquitin-conjugating enzyme E2 variant 1. Antibody reactivity to these proteins that are associated with centrosome assembly and/or microtubule function was highly associated with the diagnosis of BC. IHC staining of formalin-fixed paraffin-embedded sections with specific antibodies showed that aurora and stathmin are expressed in BC. The discovery of autoantibodies to important centrosome antigens associated with BC suggests that this immune reactivity could be related to autoimmunity developing in BC. Our finding that some of these antibodies are also present in a group of healthy women suggests that breakdown of tolerance to centrosome proteins may occur early in breast carcinogenesis and that autoantibodies to centrosome antigens might be biomarkers of early BC.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Wayne State University School of Medicine, 540 Canfield, Detroit, MI, 48201, USA, mmaroun@med.wayne.edu.
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Maroun
authors.forename: Ofelia
authors.initials: O
authors.lastname: Olivero
authors.forename: Leonard
authors.initials: L
authors.lastname: Lipovich
authors.forename: Azadeh
authors.initials: A
authors.lastname: Stark
authors.forename: Larry
authors.initials: L
authors.lastname: Tait
authors.forename: Sudeshna
authors.initials: S
authors.lastname: Bandyopadhyay
authors.forename: Matthew
authors.initials: M
authors.lastname: Burke
authors.forename: Richard
authors.initials: R
authors.lastname: Zarbo
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Chitale
authors.forename: S
authors.initials: S
authors.lastname: David Nathanson
authors.forename: Mike
authors.initials: M
authors.lastname: Long
authors.forename: Carol
authors.initials: C
authors.lastname: Peebles
authors.forename: Félix Fernández
authors.initials: FF
authors.lastname: Madrid
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism; D015551:Autoimmunity; D001943:Breast Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D061505:Cell Surface Display Techniques; D018385:Centrosome / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D018604:Epitope Mapping; D005260:Female; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice
chemical_list: D000951:Antigens, Neoplasm; D001323:Autoantibodies; D001324:Autoantigens