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Breast Cancer Research
Published in: Breast Cancer Research 6/2013

Open Access 01-12-2013 | Research article

RETRACTED ARTICLE: Progesterone receptor assembly of a transcriptional complex along with activator protein 1, signal transducer and activator of transcription 3 and ErbB-2 governs breast cancer growth and predicts response to endocrine therapy

Authors: María C Díaz Flaqué, Natalia M Galigniana, Wendy Béguelin, Rocío Vicario, Cecilia J Proietti, Rosalía Cordo Russo, Martín A Rivas, Mercedes Tkach, Pablo Guzmán, Juan C Roa, Esteban Maronna, Viviana Pineda, Sergio Muñoz, María Florencia Mercogliano, Eduardo H Charreau, Patricio Yankilevich, Roxana Schillaci, Patricia V Elizalde

Published in: Breast Cancer Research | Issue 6/2013

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Abstract

Introduction

The role of the progesterone receptor (PR) in breast cancer remains a major clinical challenge. Although PR induces mammary tumor growth, its presence in breast tumors is a marker of good prognosis. We investigated coordinated PR rapid and nonclassical transcriptional effects governing breast cancer growth and endocrine therapy resistance.

Methods

We used breast cancer cell lines expressing wild-type and mutant PRs, cells sensitive and resistant to endocrine therapy, a variety of molecular and cellular biology approaches, in vitro proliferation studies and preclinical models to explore PR regulation of cyclin D1 expression, tumor growth, and response to endocrine therapy. We investigated the clinical significance of activator protein 1 (AP-1) and PR interaction in a cohort of 99 PR-positive breast tumors by an immunofluorescence protocol we developed. The prognostic value of AP-1/PR nuclear colocalization in overall survival (OS) was evaluated using Kaplan-Meier method, and Cox model was used to explore said colocalization as an independent prognostic factor for OS.

Results

We demonstrated that at the cyclin D1 promoter and through coordinated rapid and transcriptional effects, progestin induces the assembly of a transcriptional complex among AP-1, Stat3, PR, and ErbB-2 which functions as an enhanceosome to drive breast cancer growth. Our studies in a cohort of human breast tumors identified PR and AP-1 nuclear interaction as a marker of good prognosis and better OS in patients treated with tamoxifen (Tam), an anti-estrogen receptor therapy. Rationale for this finding was provided by our demonstration that Tam inhibits rapid and genomic PR effects, rendering breast cancer cells sensitive to its antiproliferative effects.

Conclusions

We here provided novel insight into the paradox of PR action as well as new tools to identify the subgroup of ER+/PR + patients unlikely to respond to ER-targeted therapies.
Appendix
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Metadata
Title
RETRACTED ARTICLE: Progesterone receptor assembly of a transcriptional complex along with activator protein 1, signal transducer and activator of transcription 3 and ErbB-2 governs breast cancer growth and predicts response to endocrine therapy
Authors
María C Díaz Flaqué
Natalia M Galigniana
Wendy Béguelin
Rocío Vicario
Cecilia J Proietti
Rosalía Cordo Russo
Martín A Rivas
Mercedes Tkach
Pablo Guzmán
Juan C Roa
Esteban Maronna
Viviana Pineda
Sergio Muñoz
María Florencia Mercogliano
Eduardo H Charreau
Patricio Yankilevich
Roxana Schillaci
Patricia V Elizalde
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 6/2013
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr3587

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Ltbp1Lis focally induced in embryonic mammary mesenchyme, demarcates the ductal luminal lineage and is upregulated during involution
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
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