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
Identifiers and Pagination:Year: 2010
First Page: 13
Last Page: 20
Publisher Id: TOBIOMJ-3-13
Article History:Received Date: 22/05/2009
Revision Received Date: 05/09/2009
Acceptance Date: 25/09/2009
Electronic publication date: 25/3/2010
Collection year: 2010
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.
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.