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  • Original Paper
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MeCP2 and MBD2 expression during normal and pathological growth of the human mammary gland

Oncogene volume 21, pages 2704–2712 (2002)Cite this article

Abstract

During the last years, a direct link between DNA methylation and repressive chromatin structure has been established. This structural modification is mediated by histone deacetylases targeted to the methylated sequences by Methyl Binding Proteins (MBD). Human cancer cells exhibit both a global hypomethylation and some localized hypermethylations suggesting that the deregulation of the methylation machinery is a central event in tumorigenesis. Therefore, we have investigated in human tissues the expression of two major MBDs, MeCP2 and MBD2, during the proliferation of normal breast and in benign and neoplasic breast tumors. Quantitation of the transcripts indicates that MBD2 mRNAs are 20–30-fold more abundant than MeCP2 transcripts in the adult and fetal human mammary gland. In pathological tissues samples MBD2 mRNA levels are significantly higher (P=0.001) in benign tumors compared with normal breast tissues, whereas MeCP2 expression is not modified in these specimens. In neoplasic samples a deregulation of the expression of both genes was found. The amounts of MBD2 and MeCP2 transcripts vary greatly between samples in cancer cells compared to normal breast tissues or benign tumors, and in invasive ductal carcinomas the amount of MBD2 mRNA is significantly (P=0.03) associated with the tumor size. Taken together these data suggest that upregulation of MBD2 might be associated with breast cell proliferation. In line with this hypothesis MBD2 is also upregulated during the prenatal development of the human mammary gland, but in contrast to that observed in tumor cells, MeCP2 is also coordinately upregulated in the fetal breast tissues, suggesting that deregulation of MeCP2 and MBD2 occurs in human breast cancers.

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Acknowledgements

We are most grateful to Drs Alan Wolffe and Paul Wade for providing MBD2 antibodies. We thank Dr Nicole Dalla Venezia for critical reading of this manuscript. The present work was supported by the Ligue Nationale pour la Recherche contre le Cancer, Comité de Saône et Loire and Comité du Rhône and the Association pour la Recherche contre le Cancer.

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Author notes

  1. Frédérique Magdinier

    Present address: Laboratory of Molecular Biology, NIH/NIDDK. Building 5, room 214. Bethesda, Maryland, 20892, USA

  2. Gilbert M Lenoir

    Present address: Institut Gustave Roussy Villejuif, France

Authors and Affiliations

  1. Laboratoire de Génétique, UMR 5641 CNRS, UCBL1, 8 avenue Rockefeller, 69373 Lyon cedex 08, France

    Lise-Marie Billard, Frédérique Magdinier, Gilbert M Lenoir & Robert Dante

  2. Laboratoire d'anatomie pathologie, Hôpital Edouard Herriot, Lyon, France

    Lucien Frappart

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  1. Lise-Marie Billard
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Correspondence to Robert Dante.

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Billard, LM., Magdinier, F., Lenoir, G. et al. MeCP2 and MBD2 expression during normal and pathological growth of the human mammary gland. Oncogene 21, 2704–2712 (2002). https://doi.org/10.1038/sj.onc.1205357

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