Autoantibodies in Breast Cancer Identify Proteins Involved in Self- Renewal and Epigenetic Chromatin Remodeling



Félix Fernández Madrid*, 1, 4, Wei Chen2, 4, Naimei Tang1, 4, Xinbo Zhang1, 4, Jinsheng Dong1, 4, Harpreet Sagar1, 4, Judith Abrams1, 4
1 Department of Internal Medicine
2 Karmanos Cancer Institute
3 Center for Molecular Medicine and Genetics
4 Wayne State University, Detroit, Michigan, USA


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© 2010 Madrid et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the University Health Center, 4H, Department of Internal Medicine, Division of Rheumatology, Wayne State University School of Medicine, 4201 St. Antoine Blvd., Detroit, MI 48201, USA; Tel: (313) 577-1133; Fax: 313-577-1938; E-mail: fmadrid@med.wayne.edu


Abstract

Recent studies have shown that autoantibodies developing in cancer patients are tumor-associated and are promising biomarkers for the diagnosis and prognosis of cancer. Here we report a panel of signal transduction molecules with partial sequences identical to the oncogene Bmi-1, NIFK, a nucleolar protein interacting with the FHA domain of Ki- 67, TAB182, a protein interacting with tankyrase-1, CNOT6L, a subunit of the CCR4-NOT complex and to Elp3, a subunit of the elongator complex that are recognized as autoantigens by breast cancer sera with the ability to discriminate between invasive breast cancer and normal sera with high sensitivity and specificity. The proteins bearing the epitopes recognized by these antibodies have conserved regions involved in protein-protein interactions participating in regulatory processes such as self renewal, cell proliferation and survival, chromatin modulation, transcriptional silencing and organ patterning, usually ascribed to stem cell function. In this work we demonstrate by autoantigen microarray analysis that autoantibodies in breast cancer sera have the potential to delineate pathway connectivity. Our data indicate that several pathways involved in maintaining telomere stability are the target of an autoimmune reaction in breast cancer. These findings suggest that autoantibodies with the ability to recognize autoantigens involved in self-renewal and epigenetic chromatin remodeling have the potential to predict an invasive tendency of breast cancer.

Keywords: Autoantibodies, Bmi-1, autoantigen microarray, epigenetics, biomarkers, breast cancer.