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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

Oncogene volume 22, pages 3511–3517 (2003)Cite this article

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.

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Acknowledgements

We thank S Tutton for the technical assistance, and N Gebbia and RM Tomasino for the helpful discussions.

This work was supported by the Sbarro Health Research Organization and NIH grants (AG).

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Authors and Affiliations

  1. Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, PA, USA

    Marcella Macaluso, Caterina Cinti, Giuseppe Russo & Antonio Giordano

  2. Department of Oncology Section of Molecular Oncology, Regional Reference Center for the Biomolecular Characterization of Neoplasms and Genetic Screening of Hereditary Tumors, University of Palermo, Palermo, Italy

    Marcella Macaluso & Antonio Russo

  3. Institute of Normal and Pathological Cytomorphology, ITOI, CNR, Bologna, Italy

    Caterina Cinti

  4. Department of Human Pathology and Oncology, University of Siena, Siena, Italy

    Giuseppe Russo

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  1. Marcella Macaluso
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  4. Antonio Russo
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Correspondence to Antonio Giordano.

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Macaluso, M., Cinti, C., Russo, G. et al. 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. Oncogene 22, 3511–3517 (2003). https://doi.org/10.1038/sj.onc.1206578

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