title: Novel stromal biomarkers in human breast cancer tissues provide evidence for the more malignant phenotype of estrogen receptor-negative tumors.
abstract: Research efforts were focused on genetic alterations in epithelial cancer cells. Epithelial-stromal interactions play a crucial role in cancer initiation, progression, invasion, angiogenesis, and metastasis; however, the active role of stroma in human breast tumorigenesis in relation to estrogen receptor (ER) status of epithelial cells has not been explored. Using proteomics and biochemical approaches, we identified two stromal proteins in ER-positive and ER-negative human breast cancer tissues that may affect malignant transformation in breast cancer. Two putative biomarkers, T-cell receptor alpha (TCR-α) and zinc finger and BRCA1-interacting protein with a KRAB domain (ZBRK1), were detected in leukocytes of ER-positive and endothelial cells of ER-negative tissues, respectively. Our data suggest an immunosuppressive role of leukocytes in invasive breast tumors, propose a multifunctional nature of ZBRK1 in estrogen receptor regulation and angiogenesis, and demonstrate the aggressiveness of ER-negative human breast carcinomas. This research project may identify new stromal drug targets for the treatment of breast cancer patients.
authors: Department of Chemistry and Biochemistry and Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306-4390, USA.
authors: Zahraa I
authors: ZI
authors: Khamis
authors: Ziad J
authors: ZJ
authors: Sahab
authors: Stephen W
authors: SW
authors: Byers
authors: Qing-Xiang Amy
authors: QX
authors: Sang
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002853:Chromatography, Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D042783:Endothelial Cells / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D058628:Myofibroblasts / Q000378:metabolism; D010641:Phenotype; D040901:Proteomics / Q000379:methods; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000378:metabolism; D011960:Receptors, Estrogen / Q000096:biosynthesis; D012097:Repressor Proteins / Q000032:analysis / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D014408:Biomarkers, Tumor; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011960:Receptors, Estrogen; D012097:Repressor Proteins; C422407:ZNF350 protein, human