Abstract P2-08-02: Autoimmunity to centrosomal and proteasome proteins in breast cancer. A link to chromosome instability?

Abstract

Abstract BACKGROUND. Perturbation of centrosomal or centrosome-associated proteins has been observed in nearly all human solid tumors and has been implicated in the origin of chromosomal instability. Ubiquitin-proteasome degradation is highly dependent on the organizing capabilities of the centrosomes. Here we report that autoantibodies in breast cancer [BC] sera target centrosomal proteins as well as important proteins involved in proteasome protein degradation. METHODS. We immunoscreened a T7 cDNA library of BC proteins and the association of the cloned autoantigens with BC was studied by autoantigen microarray analysis. We used immunohistochemistry [IHC] to investigate the expression of the centrosome and centrosome-associated autoantigens identified. RESULTS. Immunoscreening with BC sera led to the identification of autoantibodies recognizing epitopes developing in a family of proteins located on the centrosomes such as NIMA-related kinase 7, dynein heavy chain domain 3, peri-centriolar material-1, isomorph CRA, and stathmin-1, the ubiquitin-conjugating enzyme E2, the proteasome 26S subunit and the SUMO/sentrin peptidase. Antibody reactivity to these proteins which are associated with centrosome assembly, microtubule function and protein degradation were highly associated with the diagnosis of BC. IHC staining of paraffin-embedded BC sections with specific antibodies showed that aurora and stathmin-1 and other centrosome antigens are expressed in BC. CONCLUSIONS. The discovery of autoantibodies targeting important centrosome and proteasome proteins associated with BC suggests that this immune reactivity could be related to autoimmunity developing in BC. Our findings indicate that these autoantibodies might be biomarkers of early BC and suggest the possibility of a link with chromosomal instability in BC. Citation Format: Marie-Claire Maroun, Ofelia Olivero, Judith Abrams, Wei Chen, Azadeh Stark, Carol Peebles, Larry Tait, Dhanajay Chitale, Félix Fernández Madrid. Autoimmunity to centrosomal and proteasome proteins in breast cancer. A link to chromosome instability? [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-08-02.