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.

Abstract:

: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.

journal_name

Mol Cell Biol

authors

Béguelin W,Díaz Flaqué MC,Proietti CJ,Cayrol F,Rivas MA,Tkach M,Rosemblit C,Tocci JM,Charreau EH,Schillaci R,Elizalde PV

doi

10.1128/MCB.00012-10

subject

Has Abstract

pub_date

2010-12-01 00:00:00

pages

5456-72

issue

23

eissn

0270-7306

issn

1098-5549

pii

MCB.00012-10

journal_volume

30

pub_type

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