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ADAM23, a possible tumor suppressor gene, is frequently silenced in gastric cancers by homozygous deletion or aberrant promoter hypermethylation.
Oncogene. 2005 Dec 01; 24(54):8051-60.O

Abstract

Array-based comparative genomic hybridization (CGH-array) has a powerful potential for high-throughput identification of genetic aberrations in cell genomes. We identified a homozygous loss of ADAM23 (2q33.3) in the course of a program to screen a panel of gastric cancer (GC) cell lines (1/32, 3.1%) for genomic copy-number aberrations using our custom-made CGH-array. Infrequent homozygous deletion of ADAM23 was also seen in primary gastric tumors (1/39, 2.6%). ADAM23 mRNA was expressed in normal stomach tissue, but not in the majority of GC cell lines without homozygous deletion of this gene. Expression of ADAM23 mRNA was restored to gene-silenced GC cells after treatment with 5-aza 2'-deoxycytidine. The methylation status of the ADAM23 CpG island, which showed promoter activity, correlated inversely with its expression. 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. Moreover, restoration of ADAM23 in GC cells reduced their numbers in colony-formation assays. 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.

Authors+Show Affiliations

Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

16103878

Citation

Takada, Hisashi, et al. "ADAM23, a Possible Tumor Suppressor Gene, Is Frequently Silenced in Gastric Cancers By Homozygous Deletion or Aberrant Promoter Hypermethylation." Oncogene, vol. 24, no. 54, 2005, pp. 8051-60.
Takada H, Imoto I, Tsuda H, et al. ADAM23, a possible tumor suppressor gene, is frequently silenced in gastric cancers by homozygous deletion or aberrant promoter hypermethylation. Oncogene. 2005;24(54):8051-60.
Takada, H., Imoto, I., Tsuda, H., Nakanishi, Y., Ichikura, T., Mochizuki, H., Mitsufuji, S., Hosoda, F., Hirohashi, S., Ohki, M., & Inazawa, J. (2005). ADAM23, a possible tumor suppressor gene, is frequently silenced in gastric cancers by homozygous deletion or aberrant promoter hypermethylation. Oncogene, 24(54), 8051-60.
Takada H, et al. ADAM23, a Possible Tumor Suppressor Gene, Is Frequently Silenced in Gastric Cancers By Homozygous Deletion or Aberrant Promoter Hypermethylation. Oncogene. 2005 Dec 1;24(54):8051-60. PubMed PMID: 16103878.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ADAM23, a possible tumor suppressor gene, is frequently silenced in gastric cancers by homozygous deletion or aberrant promoter hypermethylation. AU - Takada,Hisashi, AU - Imoto,Issei, AU - Tsuda,Hitoshi, AU - Nakanishi,Yukihiro, AU - Ichikura,Takashi, AU - Mochizuki,Hidetaka, AU - Mitsufuji,Shoji, AU - Hosoda,Fumie, AU - Hirohashi,Setsuo, AU - Ohki,Misao, AU - Inazawa,Johji, PY - 2005/8/17/pubmed PY - 2005/12/24/medline PY - 2005/8/17/entrez SP - 8051 EP - 60 JF - Oncogene JO - Oncogene VL - 24 IS - 54 N2 - Array-based comparative genomic hybridization (CGH-array) has a powerful potential for high-throughput identification of genetic aberrations in cell genomes. We identified a homozygous loss of ADAM23 (2q33.3) in the course of a program to screen a panel of gastric cancer (GC) cell lines (1/32, 3.1%) for genomic copy-number aberrations using our custom-made CGH-array. Infrequent homozygous deletion of ADAM23 was also seen in primary gastric tumors (1/39, 2.6%). ADAM23 mRNA was expressed in normal stomach tissue, but not in the majority of GC cell lines without homozygous deletion of this gene. Expression of ADAM23 mRNA was restored to gene-silenced GC cells after treatment with 5-aza 2'-deoxycytidine. The methylation status of the ADAM23 CpG island, which showed promoter activity, correlated inversely with its expression. 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. Moreover, restoration of ADAM23 in GC cells reduced their numbers in colony-formation assays. 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. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/16103878/ADAM23_a_possible_tumor_suppressor_gene_is_frequently_silenced_in_gastric_cancers_by_homozygous_deletion_or_aberrant_promoter_hypermethylation_ L2 - https://doi.org/10.1038/sj.onc.1208952 DB - PRIME DP - Unbound Medicine ER -