title: Activation of Stat3 by heregulin/ErbB-2 through the co-option of progesterone receptor signaling drives breast cancer growth.
abstract: 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.
authors.affiliation: Instituto de Biología y Medicina Experimental, CONICET, Obligado 2490, Buenos Aires 1428, Argentina.
authors.forename: Cecilia J
authors.initials: CJ
authors.lastname: Proietti
authors.forename: Cinthia
authors.initials: C
authors.lastname: Rosemblit
authors.forename: Wendy
authors.initials: W
authors.lastname: Beguelin
authors.forename: Martín A
authors.initials: MA
authors.lastname: Rivas
authors.forename: María Celeste
authors.initials: MC
authors.lastname: Díaz Flaqué
authors.forename: Eduardo H
authors.initials: EH
authors.lastname: Charreau
authors.forename: Roxana
authors.initials: R
authors.lastname: Schillaci
authors.forename: Patricia V
authors.initials: PV
authors.lastname: Elizalde
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D005260:Female; D015674:Mammary Neoplasms, Animal / Q000209:etiology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D020890:Neuregulin-1 / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D020890:Neuregulin-1; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; D050796:STAT3 Transcription Factor