pRb2/p130-E2F4/5-HDAC1-SUV39H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 multimolecular complexes mediate the transcription of estrogen receptor-α in breast cancer

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Abstract
The estrogen receptor-α (ER) plays a crucial role in normal breast development and is also linked to development and progression of mammary carcinoma. The transcriptional repression of ER-α gene in breast cancer is an area of active investigation with potential clinical significance. However, the molecular mechanisms that regulate the ER-α gene expression are not fully understood. Here we show a new molecular mechanism of ER-α gene inactivation mediated by pRb2/p130 in ER-negative breast cancer cells. We investigated in vivo occupancy of ER-α promoter by pRb2/p130-E2F4/5-HDAC1-SUV39 H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 complexes, and provided a link between pRb2/p130 and chromatin-modifying enzymes in the regulation of ER-α transcription in a physiological setting. These findings suggest that pRb2/p130-multimolecular complexes can be key elements in the regulation of ER-α gene expression and may be viewed as promising targets for the development of novel therapeutic strategies in the treatment of breast cancer, especially for those tumors that are ER negative.