Interaction between the fibroblast growth factor 2 (FGF2) and the progesterone receptor (PR) pathways in breast cancer

LANARI, CLAUDIA; SAHORES, ANA; FIGUEROA, VIRGINIA; LAMB, CAROLINE

Mar del Plata

Congreso; Sociedad Argentina de Investigación Clínica; 2016

About 75% of all breast cancers express hormone receptors and these patients are eligible to receive endocrine therapy. However, some patients are unresponsive or develop resistance to hormone therapy. Dysregulation of the FGF2/FGFR signaling pathway has been associated with different types of cancer. In humans, FGF2 consists of five protein isoforms with different molecular weights: 18 kDa (low molecular weight, LMW-FGF2) and 22, 22.5, 24 and 34 kDa (high molecular weight, HMW-FGF2). In murine and human breast cancer models, we demonstrated that tumor variants resistant to the antiprogestin mifepristone (MFP), express a higher PR isoform B/isoform A ratio compared to responsive tumors. We recently observed that hormone resistant variants also express higher levels of HMW-FGF2. Our aim is to investigate the interaction between the PR and FGF2/FGFR pathways in order to determine the mechanisms that drive breast cancer progression. We worked with the T47D human cell line that expresses high levels of PR, low levels of HMW-FGF2 and responds to MFP treatment. We infected T47D cells with plasmid constructions containing an empty vector, a sequence for the 18 or the 22 kDa FGF2 isoforms. We found that T47D-18 and -22 were unresponsive or increased cell proliferation (p