TRASTUZUMAB REGULATES SRC/FAK/PAXILLIN KINASES CONTROLLING ErbB-2 HUMAN BREAST CANCER CELL MOTILITY.

MONDACA JM; FLAMINI MI; SANCHEZ AM

Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

Breast cancer is the most common cancer in women worldwide. The majority of deaths attributed to breast cancer are a result from metastasis. Breast carcinoma is classified into molecular subtypes according to the presence and/or absence of estrogen receptors (ER¬), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). HER2+ breast cancers represent 20-25% of all breast cancer diagnoses. Currently, new anti-HER2 strategies that are used in clinical studies have been developed. One of these strategies is a monoclonal antibody that binds to the extracellular domain of HER2 known as Trastuzumab (Tz). In addition, dimerization of HER2/HER3 receptors regulates diverse cellular functions, including cellular motility. Heregulin (HRG), a HER3 ligand plays a role in the development and progression of breast cancer. However, HRG effects on cell motility have not been fully explored in breast cancer cells. Therefore, the aim of our work is to identify new molecular mechanisms regulated by HRG/Tz on the morphology and motility of BT-474 (HER2+) cells, a Tz-sensitive human breast cancer cell line. We observed in HER2+ cells that, the treatment with HRG (1nM) induced firstly, a significantly phosphorylation/activation and dimerization of HER2/HER3 receptor (p