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Istituto di scienza dell'alimentazione

Torna all'elenco Contributi in rivista anno 2013

Contributo in rivista

Tipo: Articolo in rivista

Titolo: Retinoic acid impairs estrogen signaling in breast cancer cells by interfering with activation of LSD1 via PKA

Anno di pubblicazione: 2013

Formato: Elettronico Cartaceo

Autori: Maria Neve Ombra a, Annalisa Di Santi b, Ciro Abbondanza b, Antimo Migliaccio b, Enrico Vittorio Avvedimento c, Bruno Perillo a.

Affiliazioni autori: a Istituto di Scienze dell'Alimentazione, C.N.R., 83100 Avellino, Italy b Dipartimento di Patologia Generale, Seconda Università degli Studi di Napoli, 80138 Naples, Italy c Dipartimento di Biologia e Patologia Cellulare e Molecolare "L. Califano", Università degli Studi "Federico II", 80131 Naples, Italy

Autori CNR:


Lingua: inglese

Abstract: More than 70% of breast cancers in women require estrogens for cell proliferation and survival. 17?-estradiol (E2) effect on mammary target cells is almost exclusively mediated by its binding to the estrogen receptor-? (ER?) that joins chromatin where it assembles active transcription complexes. The proliferative and pro-survival action of estrogens is antagonized in most cases by retinoic acid (RA), even though the cognate retinoic acid receptor-? (RAR?) cooperates with ER? on promoters of estrogen-responsive genes. We have examined at the molecular level the crosstalk between these nuclear receptors from the point of view of their control of cell growth and show here that RA reverts estrogen-stimulated transcription of the pivotal anti-apoptotic bcl-2 gene by preventing demethylation of dimethyl lysine 9 in histone H3 (HeK9me2). As we previously reported, this is obtained by means of E2-triggered activation of the lysine-specific demethylase 1 (LSD1), an enzyme that manages chromatin plasticity in order to allow specific movements of chromosomal regions within the nucleus. We find that E2 fuels LSD1 by inducing migration of the catalytic subunit of protein kinase A (PKA) into the nucleus, where it targets estrogen-responsive loci. RA rescues LSD1-dependent disappearance of H3K9me2 at bcl-2 regulatory regions upon the prevention of PKA assembly to the same sites.

Lingua abstract: inglese

Pagine da: 480

Pagine a: 486


Biochimica et biophysica acta. Gene regulatory mechanisms Elsevier
Paese di pubblicazione: Paesi Bassi
Lingua: inglese
ISSN: 1874-9399

Numero volume: 1829

Numero fascicolo: 5

DOI: 10.1016/j.bbagrm.2013.03.003

Referee: Sì: Internazionale

Indicizzato da: Science direct - Elsevier [S1874939913000485]

URL: http://dx.doi.org/10.1016/j.bbagrm.2013.03.003

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