Activation of Stat3 by Heregulin/ErbB-2 through the Co-Option of Progesterone Receptor Signaling Drives Breast Cancer Growth

作者：Proietti Cecilia J; Rosemblit Cinthia; Beguelin Wendy; Rivas Martin A; Diaz Flaque Maria Celeste; Charreau Eduardo H; Schillaci Roxana; Elizalde Patricia V^*

来源：Molecular and Cellular Biology, 2009, 29(5): 1249-1265.

DOI：10.1128/MCB.00853-08

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.

• 出版日期2009-3-1