Activation of Stat3 by heregulin/ErbB-2 through the co-option of progesterone receptor signaling drives breast cancer growth.

PROIETTI CJ; ROSEMBLIT C; BEGUELIN W; RIVAS MA; DÍAZ FLAQUÉ MC; CHARREAU EH; SCHILLACI R; ELIZALDE PV

MOLECULAR AND CELLULAR BIOLOGY

AMER SOC MICROBIOLOGY

Año: 2009 vol. 29 p. 1249 - 1265

0270-7306

Cross talk between the steroid hormone receptors for estrogen and progesterone (PR) and the ErbB family of receptor tyrosine kinases appears to be a hallmark of breast cancer growth, but its underlying mechanism remains poorly explored. Here we have highlighted signal transducer and activator of transcription 3 (Stat3) as a key protein activated by heregulin (HRG), a ligand of the ErbB receptors, through co-opted, ligand-independent PR function as a signaling molecule. Stat3 activation was an absolute requirement in HRG-induced mammary tumor growth, and targeting Stat3 effectively inhibited growth of breast cancer cells with activated HRG/ErbB-2 and PR. Our findings unravel a novel potential therapeutic intervention in PR- and ErbB-2-positive breast tumors, involving the specific blockage of PR signaling activity.