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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References
Bird AP and Wolffe AP . (1999). Cell, 99, 451–454.
Cameron EE, Bachman KE, Myohanen S, Herman J and Baylin SB . (1999). Nat. Genet., 21, 103–107.
Davis T, Kennedy C, Chiew YE, Clarke CL and deFazio A . (2000). Clin. Cancer Res., 6, 4334–4342.
Dunaief JL, Strober BE, Guha S, Khavari PA, Alin K, Luban J, Begemann M, Crabtree GR and Goff SP . (1994). Cell, 79, 119–130.
Ferreira R, Magnaghi-Jaulin L, Robin P, Harel-Bellan A and Trouche D . (1998). Proc. Natl. Acad. Sci. USA, 95, 10493–10498.
Grunstein M . (1997). Nature, 389, 349–352.
Hayes JJ and Hansen JC . (2001). Curr. Opin. Genet. Dev., 11, 124–129.
Hortobagyi GN . (1998). N. Engl. J. Med., 339, 974–984.
Iavarone A and Massague J J . (1999). Mol. Cell. Biol., 19, 916–922.
Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU, Landsberger N, Strouboulis J and Wolffe AP . (1998). Nat. Genet., 19, 187–191.
Keller C, Ladenburger EM, Kremer M and Knippers R . (2002). J Biol. Chem., 277, 31430–31440.
Laird PW and Jaenisch R . (1996). Annu. Rev. Genet., 30, 441–464.
Lapidus RG, Nass SJ, Butash KA, Parl FF, Weitzman SA, Graff JG, Herman JG and Davidson NE . (1998). Cancer Res., 58, 2515–2519.
La Sala D, Macaluso M, Trimarchi C, Giordano A and Cinti C . (2003). Oncogene, 22, 3518–3529.
Lin RJ, Nagy L, Inoue S, Shao W, Miller Jr WH and Evans RM . (1998). Nature, 391, 811–814.
Magnaghi-Jaulin L, Groisman R, Naguibneva I, Robin P, Lorain S, Le Villain JP, Troalen F, Trouche D and Harel-Bellan A . (1998). Nature, 391, 601–605.
Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN and Bird A . (1998). Nature, 393, 386–389.
Ng HH and Bird A . (1999). Curr. Opin. Genet. Dev., 9, 158–163.
Orlando V, Strutt H and Paro R . (1997). Methods, 11, 205–214.
Osborne CK . (1998). Breast Cancer Res. Treat., 51, 227–238.
Parl FF . (2000). Estrogens, Estrogen Receptors, and Breast Cancer. IOS Press: Amsterdam.
Robertson KD, Ait-Si-Ali S, Yokochi T, Wade PA, Jones PL and Wolffe AP . (2000). Nat. Genet., 25, 338–342.
Rountree MR, Bachman KE and Baylin SB . (2000). Nat. Genet., 25, 269–277.
Sif S, Saurin AJ, Imbalzano AN and Kingstonm RE . (2001). Genes Dev., 15, 603–618.
Stiegler P, De Luca A, Bagella L and Giordano A . (1998). Cancer Res., 58, 5049–5052.
Strahl BD and Allis CD . (2000). Nature, 403, 41–45.
Struhl K . (1998). Genes Dev., 12, 599–606.
Trouche D, Le Chalony C, Muchardt C, Yaniv M and Kouzarides T . (1997). Proc. Natl. Acad. Sci. USA, 94, 11268–11273.
Vandel L, Nicolas E, Vaute O, Ferreira R, Ait-Si-Ali S and Trouche D . (2001). Mol. Cell. Biol., 21, 6484–6494.
Vignali M, Hassan AH, Neely KE and Workman JL . (2000). Mol. Cell. Biol., 20, 1899–1910.
Weigel RJ and de Coninck EC . (1993). Cancer Res., 53, 3472–3474.
West M, Blanchette C, Dressman H, Huang E, Ishida S, Spang R, Zuzan H, Olson Jr JA, Marks JR and Nevins JR . (2001). Proc. Natl. Acad. Sci. USA, 98, 11462–11467.
Yang X, Ferguson AT, Nass SJ, Phillips DL, Butash KA, Wang SM, Herman JG and Davidson NE . (2000). Cancer Res., 60, 6890–6894.
Yang X, Phillips DL, Ferguson AT, Nelson WG, Herman JG and Davidson NE . (2001). Cancer Res., 61, 7025–7029.
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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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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DOI: https://doi.org/10.1038/sj.onc.1206578
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