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

被引：82
作者：
Beguelin, Wendy [1 ]
Diaz Flaque, Maria Celeste [1 ]
Proietti, Cecilia J. [1 ]
Cayrol, Florencia [1 ]
Rivas, Martin A. [1 ]
Tkach, Mercedes [1 ]
Rosemblit, Cinthia [1 ]
Tocci, Johanna M. [1 ]
Charreau, Eduardo H. [1 ]
Schillaci, Roxana [1 ]
Elizalde, Patricia V. [1 ]
机构：
[1] Consejo Nacl Invest Cient & Tecn, IBYME, Lab Mol Mech Carcinogenesis, Buenos Aires, DF, Argentina
来源：
MOLECULAR AND CELLULAR BIOLOGY | 2010年 / 30卷 / 23期
关键词：
CELL-PROLIFERATION; SIGNAL TRANSDUCER; CYCLIN D1; IN-VIVO; UP-REGULATION; ACTIVATION; SRC; PROTEIN; GENE; MECHANISM;
D O I：
10.1128/MCB.00012-10
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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-2 nuclear translocation and the assembly of a transcriptional complex in which ErbB-2 acts as a coactivator of Stat3. We also highlighted that the function of ErbB-2 as a Stat3 coactivator drives progestin-induced cyclin D1 promoter activation. Notably, PR is also recruited together with Stat3 and ErbB-2 to the cyclin D1 promoter, unraveling a new and unexpected nonclassical PR genomic mechanism. The assembly of the nuclear Stat3/ErbB-2 transcriptional complex plays a key role in the proliferation of breast tumors with functional PR and ErbB-2. Our findings reveal a novel therapeutic intervention for PR-and ErbB-2-positive breast tumors via the specific blockage of ErbB-2 nuclear translocation.
引用
收藏
页码：5456 / 5472
页数：17
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