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Istituto di scienza dell'alimentazione

Torna all'elenco Contributi in rivista anno 2006

Contributo in rivista

Tipo: Articolo in rivista

Titolo: Comparative gene expression profiling reveals partially overlapping but distinct genomic actions of different antiestrogens in human breast cancer cells.

Anno di pubblicazione: 2006

Autori: Scafoglio C., Ambrosino C., Cicatiello L., Altucci L., Ardovino M., Bontempo P., Medici N., Molinari A.M., Nebbioso A., Facchiano A., Calogero R.A., Elkon R., Menini N., Ponzone R., Biglia N., Sismondi P., De Bortoli M., and Weisz A.

Affiliazioni autori: 1 Dipartimento di Patologia generale, Seconda UniversitÓ degli Studi di Napoli, Vico L. De Crecchio 7, 80138 Napoli, Italy 2 AIRC Naples Oncogenomics Center, c/o CEINGE Biotecnologia Avanzate, Napoli, Italy 3 Istituto di Scienze dell'Alimentazione del Consiglio Nazionale delle Ricerche, Avellino, Italy 4 Dipartimento di Scienze Cliniche e Biologiche, UnitÓ di Genomica e Bioinformatica, UniversitÓ degli Studi di Torino, Orbassano, Italy 5 Department of Human Genetics and Molecular Medicine, The David and Inez Myers Laboratory for Genetic Research, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel 6 Dipartimento di Scienze Oncologiche, Istituto per la Ricerca e la Cura del Cancro,UniversitÓ degli Studi di Torino, Candiolo, Italy 7 UnitÓ di Ginecologia Oncologica, Istituto per la Ricerca e la Cura del Cancro,UniversitÓ degli Studi di Torino, Candiolo, Italy

Autori CNR:


Lingua: inglese

Abstract: Antiestrogens used for breast cancer (BC) treatment differ among each other for the ability to affect estrogen receptor (ER) activity and thereby inhibit hormone-responsive cell functions and viability. We used high-density cDNA microarrays for a comprehensive definition of the gene pathways affected by 17beta-estradiol (E2), ICI 182,780 (ICI), 4OH-tamoxifen (Tamoxifen), and raloxifene (RAL) in ER-positive ZR-75.1 cells, a suitable model to investigate estrogen and antiestrogen actions in hormone-responsive BC. The expression of 601 genes was significantly affected by E2 in these cells; in silico analysis reveals that 86 among them include one or more potential ER binding site within or near the promoter and that the binding site signatures for E2F-1, NF-Y, and NRF-1 transcription factors are significantly enriched in the promoters of genes induced by estrogen treatment, while those for CAC-binding protein and LF-A1 in those repressed by the hormone, pointing to novel transcriptional effectors of secondary responses to estrogen in BC cells. Interestingly, expression of 176 E2-regulated mRNAs was unaffected by any of the antiestrogens tested, despite the fact that under the same conditions the transcriptional and cell cycle stimulatory activities of ER were inhibited. On the other hand, of 373 antiestrogen-responsive genes identified here, 52 were unresponsive to estrogen and 25% responded specifically to only one of the compounds tested, revealing non-overlapping and clearly distinguishable effects of the different antiestrogens in BC cells. As some of these differences reflect specificities of the mechanism of action of the antiestrogens tested, we propose to exploit this gene set for characterization of novel hormonal antagonists and selective estrogen receptor modulators (SERMs) and as a tool for testing new associations of antiestrogens, more effective against BC. (c) 2006 Wiley-Liss, Inc.

Lingua abstract: inglese

Pagine da: 1163

Pagine a: 1184


Journal of cellular biochemistry Wiley-Liss
Paese di pubblicazione: Stati Uniti d'America
Lingua: inglese
ISSN: 0730-2312

Numero volume: 98

DOI: 10.1002/jcb.20820

Indicizzato da: PubMed [16514628]

URL: http://onlinelibrary.wiley.com/doi/10.1002/jcb.20820/abstract

Altre informazioni: 6

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