The regulation of ER-alpha transcription by pRb2/p130 in breast cancer.
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 (17beta-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.
Macaluso
M
M
Sbarro Institute for Cancer Research and Molecular Medicine, Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA.
Montanari
M
M
Giordano
A
A
D001943:Breast Neoplasms / Q000235:genetics*; D050719:Crk-Associated Substrate Protein / Q000502:physiology*; D019175:DNA Methylation; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D006801:Humans; D055273:Salivary Proline-Rich Proteins; D012471:Salivary Proteins and Peptides / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology
C493841:BCAR1 protein, human; D050719:Crk-Associated Substrate Protein; D047628:Estrogen Receptor alpha; C524745:PRB2 protein, human; D055273:Salivary Proline-Rich Proteins; D012471:Salivary Proteins and Peptides