Disease relevance of ADAM23

• ADAM23, a possible tumor suppressor gene, is frequently silenced in gastric cancers by homozygous deletion or aberrant promoter hypermethylation [1].
• ADAM23 methylation and expression analysis in brain tumors [2].
• In this work, we have examined the expression level and the methylation status of the 5' upstream region of the adhesion molecule ADAM23 in two brain tumor cell lines (A172 and T98G) as well as in three primary brain tumors (one grade II astrocytoma and two meningiomas) and 15 glioblastoma xenografts [2].
• Together, these results indicate that ADAM23 down-regulation by methylation in brain tumors is a rare event and it may help explain why brain tumor metastases are rarely found elsewhere in the body [2].
• On the basis of these results, we propose that ADAM 23, through its disintegrin-like domain, may function as an adhesion molecule involved in alphavbeta3-mediated cell interactions occurring in normal and pathological processes, including progression of malignant tumors from neural origin [3].

High impact information on ADAM23

• In this work we show that the disintegrin-like domain of ADAM 23 produced in Escherichia coli and immobilized on culture dishes promotes attachment of different human cells of neural origin, such as neuroblastoma cells (NB100 and SH-S(y)5(y)) or astrocytoma cells (U373 and U87 MG) [3].
• ADAM 23/MDC3, a human disintegrin that promotes cell adhesion via interaction with the alphavbeta3 integrin through an RGD-independent mechanism [3].
• ADAM 23 (a disintegrin and metalloproteinase domain)/MDC3 (metalloprotease, disintegrin, and cysteine-rich domain) is a member of the disintegrin family of proteins expressed in fetal and adult brain [3].
• Analysis of ADAM 23 binding to integrins revealed a specific interaction with alphavbeta3, mediated by a short amino acid sequence present in its putative disintegrin loop [3].
• The methylation status of the ADAM23 CpG island, which showed promoter activity, correlated inversely with its expression [1].

Biological context of ADAM23

• Human chromosomal mapping indicated that ADAM22 and ADAM23 mapped to chromosome 7q21 and 2q33, respectively, while the three pseudogenes 1-2, 3-3, and 1-32 mapped to chromosome 14q24.1, 8p23, and 14q24.1, respectively [4].
• These results suggest that genetic or epigenetic silencing by hypermethylation of the ADAM23 CpG-rich promoter region leads to loss of ADAM23 function, which may be a factor in gastric carcinogenesis [1].
• However, we were unable to detect methylation and down-regulation of the ADAM23 gene in brain tumors [2].

Anatomical context of ADAM23

• ADAM23 mRNA was expressed in normal stomach tissue, but not in the majority of GC cell lines without homozygous deletion of this gene [1].

Associations of ADAM23 with chemical compounds

• Expression of ADAM23 mRNA was restored to gene-silenced GC cells after treatment with 5-aza 2'-deoxycytidine [1].
• Using bisulfite sequencing we verified that the percentage of methylated dinucleotides is higher in T98G when compared to A172 and that methylation significantly correlates with ADAM23 mRNA and protein expression [2].

Other interactions of ADAM23

• Methylation of this CpG island was observed both in GC cell lines and in primary GC tissues; in primary tumors with a hypermethylated CpG island, expression of ADAM23 was lower than in adjacent noncancerous tissues [1].

Analytical, diagnostic and therapeutic context of ADAM23

• In this paper, we report the cloning and sequence analysis of two novel additional members of this family, which we have termed MDC2 and MDC3 [5].

References