MAMMARY CARCINOMA-ASSOCIATED FIBROBLASTS AS KEY PLAYERS IN THE ACQUISITION OF HORMONE-INDEPENDENCE: INTERACTION BETWEEN PROGESTERONE RECEPTORS AND FIBROBLAST GROWTH FACTOR RECEPTOR 2

LANARI C; LAMB CA; CERLIANI JP; GIULIANELLI S; NOVARO V; FABRIS VT; BOTTINO MC; SOLDATI R; WARGON V; MOLINOLO AA

MEDICINA (BUENOS AIRES)

MEDICINA (BUENOS AIRES)

Año: 2007 vol. 67 p. 65 - 69

0025-7680

We have developed an experimental model of mouse mammary carcinomas expressing high levels of hormone receptors which transit through different stages of hormone dependence. In this study we have demonstrated that carcinoma associated fibroblasts (CAF) from hormone independent tumors (HI) express higher levels of FGF-2 than those of hormone-dependent tumors. Stromal FGF-2 activates FGFR-2 in the epithelial cells which in turn activates progesterone receptors (PR) and induces cell proliferation. In addition we showed nuclear interaction of FGFR-2 and PR suggesting novel cross talk mechanisms between both pathways. These results were reproduced in the T47D human breast cancer cells. Our data indicate that stroma participates in HI tumor growth and that the FGF-2- FGFR-2 axis should be considered as a therapeutic target together with antiprogestins in PR positive breast cancer.