Progesterone receptor induces ErbB-2 nuclear translocation to promote breast cancer growth via a novel transcriptional effect: ErbB-2 function as a coactivator of Stat3.

WENDY BEGUELIN; MARÍA C. DÍAZ FLAQUÉ; CECILIA J. PROIETTI; FLORENCIA CAYROL; MARTÍN A. RIVAS; MERCEDES TKACH; CINTHIA ROSEMBLIT; JOHANA TOCCI; EDUARDO H. CHARREAU; ROXANA SCHILLACI; PATRICIA V. ELIZALDE

MOLECULAR AND CELLULAR BIOLOGY

AMER SOC MICROBIOLOGY

Año: 2010 vol. 30 p. 5456 - 5472

0270-7306

Progesterone receptor (PR) and ErbB-2 bidirectional cross talk participates in breast cancer development.Here, we identified a new mechanism of the PR and ErbB-2 interaction involving the PR induction of ErbB-2nuclear translocation and the assembly of a transcriptional complex in which ErbB-2 acts as a coactivator ofStat3. We also highlighted that the function of ErbB-2 as a Stat3 coactivator drives progestin-induced cyclinD1 promoter activation. Notably, PR is also recruited together with Stat3 and ErbB-2 to the cyclin D1promoter, unraveling a new and unexpected nonclassical PR genomic mechanism. The assembly of the nuclearStat3/ErbB-2 transcriptional complex plays a key role in the proliferation of breast tumors with functional PRand ErbB-2. Our findings reveal a novel therapeutic intervention for PR- and ErbB-2-positive breast tumorsvia the specific blockage of ErbB-2 nuclear translocation.