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Annals of Oncology 2005 16(Supplement 4):iv20-iv22; doi:10.1093/annonc/mdi903
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© 2005 European Society for Medical Oncology

Invited Paper

The regulation of ER-{alpha} transcription by pRb2/p130 in breast cancer

M. Macaluso1,2,3, M. Montanari1,4 and A. Giordano1,3,*

1 Sbarro Institute for Cancer Research and Molecular Medicine, Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA; 2 Department of Oncology; University of Palermo, Palermo; 3 Department of Human Pathology and Oncology University of Siena, Siena; 4 Istituto di Patologia Generale-Centro di Ricerche Oncologiche Giovanni XXIII, Catholic University of Sacred Heart, Roma, Italy

* Correspondence to: A. Giordano, Sbarro Institute for Cancer Research and Molecular Medicine, Center of Biotechnology, College of Science and Technology, Temple University, 19122-Philadelphia, PA, USA; Email: giordano{at}temple.edu

Breast carcinoma is the most common form of neoplasia in women of the Western world, and the mortality from this disease in women is second only to that of lung cancer, with a means incidence of 10%. Although, several studies have indicated that the development of this fairly heterogeneous disease depends on a great many environmental, socio-economic, hormonal and genetic factors, the pathogenesis of breast cancer remains poorly understood.

ER-{alpha} (estrogen-receptor alpha) and its ligand (17ß-estradiol) play a crucial role in normal breast development and have also been linked to mammary carcinogenesis and clinical outcome in breast cancer patients. The estrogen signaling regulates the growth of some breast tumors, and antiestrogen therapies can effectively block this growth signaling resulting in tumor suppression. However, most tumors eventually develop antiestrogen resistance, and antiestrogen are mostly ineffective in patience with advanced disease. Although several studies have been proposed that epigenetic events could be involved in ER-{alpha} silencing the mechanisms regulating ER-{alpha} transcription are poorly understood. Our studies suggested that pRb2/p130-complexes bind to the ER-{alpha} promoter and could be involved in the transcriptional regulation of the ER-{alpha} gene by altering chromatin structure and DNA methylation pattern.

Key words: breast cancer, ER-{alpha} transcription, pRb2/p130, chromatin remodeling enzymes, DNA methylation


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