Intrinsic FGF2 induces endocrine resistance in breast cancer: Differential role between low and high molecular weight FGF2 isoforms in tumor progression

LANARI CLAUDIA; SEQUEIRA GONZALO; MAY MARÍA; LAMB CAROLINE; ÁLVAREZ MICHELLE; ABBA MARTIN; SAHORES ANA; MOLINOLO ALFREDO; JACOBSEN BRITTA; FIGUEROA VIRGINIA

Conferencia; Gordon Research Conference, Frontiers of Science.; 2017

Endocrine resistance remains a major clinical challenge in patients with luminal breast cancer. A possible role of the progesterone receptors (PR), and its isoforms PRA and PRB as mediators in this progression remains still controversial1. We previously demonstrated that endocrine resistant tumors express a low PRA/PRB ratio2, and is a prognostic and predictive factor for antiprogestin responsiveness in breast cancer3.A proposed potential mechanism for resistance is the dysregulation of growth factor signaling pathways such as FGF4. FGF2 in particular consists of several isoforms of low (LMW) and high molecular weight (HMW). LMW-FGF2 is essentially a secreted protein, and HMW-FGF2 isoforms are mainly located in the cell nuclei. FGF2 classically signals through membrane FGFR, activating intracellular pathways involved in different cellular functions5. In cancer, much attention has been paid to genomic alterations in FGFR and its paracrine or autocrine activation by LMW-FGF2, while the role of intracellular FGF2 still remains poorly understood. A handful of studies have addressed a possible relationship between HMW-FGF2 overexpression with chemo- and radioresistance in cancer6-7, but a role in hormone resistance in breast cancer remains unexplored.