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  • Oncogenomics
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Epigenetic silencing of the adhesion molecule ADAM23 is highly frequent in breast tumors

Oncogene volume 23, pages 1481–1488 (2004)Cite this article

Abstract

Altered cell adhesion is causally involved in tumor progression, and the identification of novel adhesion molecules altered in tumors is crucial for our understanding of tumor biology and for the development of new prognostic and therapeutic strategies. Here, we provide evidence for the epigenetic downregulation in breast tumors of the A Desintegrin And Metalloprotease domain 23 gene (ADAM 23), a member of a new family of surface molecules with roles in cell–cell adhesion and/or cell–matrix interactions. We examined the mRNA expression and methylation status of the 5′ upstream region of the ADAM23 gene in different breast tumor cell lines as well as in primary breast tumors. We found ADAM23 5′ hypermethylation in eight out of 12 (66.7%) tumor cell lines and in nine out of 13 (69.2%) primary tumors. Promoter hypermethylation was strongly associated with reductions in both mRNA and protein expression, with a threshold of 40–60% of modified CpG dinucleotides being required for the complete silencing of ADAM23 mRNA expression. Treatment of MCF-7 and SKBR-3 cell lines with 5′-Aza-2′-deoxycytidine led to a reactivation of ADAM23 mRNA expression and a marked decrease in the methylation level. It is worth noting that primary breast tumors with a more advanced grade showed a higher degree of methylation, suggesting that the adhesion molecule ADAM23 may be downregulated during the progression of breast cancer.

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Abbreviations

ADAM:

A Desintegrin And Metalloprotease domain

MDC:

Metalloprotease/Disintegrin/Cysteine rich

TACE:

TNF-α converting enzyme

TNF-α:

tumor necrosis factor-α

CAM:

cell adhesion molecule

5′-Aza-dCR:

5′-Aza-2′-deoxycytidine

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Acknowledgements

We thank Dr Ricardo R Brentani, Dr Roger Chamas, Dr Luís F Reis, Dr Dirce M Carraro and Dr Eduardo F Abrantes for critically reading this manuscript and Valéria Paixão, Marilene H Lopes and Waleska K Martins for technical assistance. This work was supported by The Ludwig Institute for Cancer Research (LICR) – São Paulo – Brazil and by the CEPID Program from the Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP). FFC is sponsored by a fellowship from FAPESP.

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Authors and Affiliations

  1. Laboratory of Molecular Biology and Genomics, Ludwig Institute for Cancer Research, SP, Brazil

    Fabrício F Costa, Newton V Verbisck, Anna Christina M Salim, Daniela F Ierardi, Lilian C Pires, Andrew JG Simpson & Anamaria A Camargo

  2. Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, SP, Brazil

    Regina M Sasahara & Mari C Sogayar

  3. Laboratório de Neurobiologia, Universidade Federal do Paraná, PR, Brazil

    Silvio M Zanata

  4. Breast Cancer Laboratory, Ludwig Institute for Cancer Research, University College, England

    Alan Mackay & Michael O'Hare

  5. Departamento de Patologia, Hospital ACCamargo, SP, Brazil

    Fernando Soares

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  1. Fabrício F Costa
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Correspondence to Anamaria A Camargo.

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Costa, F., Verbisck, N., Salim, A. et al. Epigenetic silencing of the adhesion molecule ADAM23 is highly frequent in breast tumors. Oncogene 23, 1481–1488 (2004). https://doi.org/10.1038/sj.onc.1207263

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