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

• Published in: Oncogene Vol. 23; no. 7; pp. 1481 - 1488
• Main Authors: COSTA, Fabricio F, VERBISCK, Newton V, SOARES, Fernando, SIMPSON, Andrew J. G, CAMARGO, Anamaria A, SALIM, Anna Christina M, IERARDI, Daniela F, PIRES, Lilian C, SASAHARA, Regina M, SOGAYAR, Mari C, ZANATA, Silvio M, MACKAY, Alan, O'HARE, Michael
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 19.02.2004; Nature Publishing Group
• Subjects: ADAM Proteins; Androgens; Biological and medical sciences; Breast cancer; Breast Neoplasms - metabolism; Cancer research; Cell adhesion; Cell adhesion & migration; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; CpG islands; Disintegrins - genetics; Disintegrins - metabolism; DNA Methylation; Down-Regulation; Epigenesis, Genetic - physiology; Epigenetics; Female; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Silencing - physiology; Genomics; Growth factors; Humans; Medical prognosis; Medical research; Metalloendopeptidases - genetics; Metalloendopeptidases - metabolism; Metalloproteinase; Metastasis; Molecular and cellular biology; Molecular biology; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Promoter Regions, Genetic; RNA, Messenger - metabolism; Tumor cell lines; Tumor necrosis factor-TNF; Tumors; Brazil; breast tumor; cell adhesion; downregulation; ADAM23; Epigenetics; Tumor; Mammary gland; Methylation; Adhesion; Carcinogenesis
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1207263

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. Oncogene (2004) 23, 1481-1488. doi:10.1038/sj.onc.1207263 Published online 8 December 2003