CHARACTERIZATION OF A TRASTUZUMAB-RE SISTANT HER2-OVEREXPRESSING BREAST CANCER CELL MODEL USING SHOTGUN PROTEOMICS

ABRIGO M; WOLOS VJ; TAPIA IJ; DIAMENT M; BAL DE KIER JOFFÉ ED; LACUNZA E; FISZMAN GL

Congreso; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022; 2022

HER2 is overexpressed in 15-20% human breast tumors and is associated with poor disease-free survival. Trastuzumab (Tz), a HER2-targeted monoclonal antibody, is the therapy of choice forHER2+ breast cancer patients. However, more than half of them develop resistance during treatment. In our laboratory, we established a Tz-resistant breast cancer cell line, BT-474R, obtained by continuous treatment of HER2+ BT-474 cell line with 10 µg/ml Tz for 6 months. The aim of this work was to identify protein profiles associated with the resistant phenotype. To this end, we compared BT- 474 and BT-474R through a LFQ proteomic approach. A label-free mass spectrometric protein quantification followed by Proteome Discoverer analyses was performed (FDR 1%). For differential protein expression analysis, we employed DEqMS in R/Bioconductor. Results were visualized in a Volcano plot (fold change=2). We identified 176 differentially abundant proteins from a total of 1,381, among which 62 were upregulated and 114 downregulated in BT- 474R cells (p