An Estrogen Receptor-α/p300 Complex Activates the BRCA-1 Promoter at an AP-1 Site That Binds Jun/Fos Transcription Factors: Repressive Effects of p53 on BRCA-1 Transcription1
| Autor: | Jeffy, Brandon D, Hockings, Jennifer K, Kemp, Michael Q, Morgan, Sherif S, Hager, Jill A, Beliakoff, Jason, Whitesell, Luke J, Bowden, G. Timothy, Romagnolo, Donato F |
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| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
animal structures
endocrine system diseases Transcription Genetic BRCA1 Protein Proto-Oncogene Proteins c-jun Estrogen Receptor alpha Estrogens DNA Neoplasm HCT116 Cells Transcription Factor AP-1 Cell Line Tumor Humans Tumor Suppressor Protein p53 skin and connective tissue diseases Promoter Regions Genetic E1A-Associated p300 Protein Proto-Oncogene Proteins c-fos Research Article HeLa Cells Transcription Factors |
| Popis: | One of the puzzles in cancer predisposition is that women carrying BRCA-1 mutations preferentially develop tumors in epithelial tissues of the breast and ovary. Moreover, sporadic breast tumors contain lower levels of BRCA-1 in the absence of mutations in the BRCA-1 gene. The problem of tissue specificity requires analysis of factors that are unique to tissues of the breast. For example, the expression of estrogen receptor-alpha (ER alpha) is inversely correlated with breast cancer risk, and 90% of BRCA-1 tumors are negative for ER alpha. Here, we show that estrogen stimulates BRCA-1 promoter activity in transfected cells and the recruitment of ER alpha and its cofactor p300 to an AP-1 site that binds Jun/Fos transcription factors. The recruitment of ER alpha/p300 coincides with accumulation in the S-phase of the cell cycle and is antagonized by the antiestrogen tamoxifen. Conversely, we document that overexpression of wild-type p53 prevents the recruitment of ER alpha to the AP-1 site and represses BRCA-1 promoter activity. Taken together, our findings support a model in which an ER alpha/AP-1 complex modulates BRCA-1 transcription under conditions of estrogen stimulation. Conversely, the formation of this transcription complex is abrogated in cells overexpressing p53. |
| Databáze: | OpenAIRE |
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