RRC ID 71718
Author Iida S, Akiyama Y, Nakajima T, Ichikawa W, Nihei Z, Sugihara K, Yuasa Y.
Title Alterations and hypermethylation of the p14(ARF) gene in gastric cancer.
Journal Int J Cancer
Abstract p14(ARF), generated through an alternative splicing process that replaces the first exon, 1alpha, of p16(INK4a) with exon 1beta, located >15 kb upstream of exon 1alpha, has been shown to function as a growth suppressor. We examined 11 gastric cancer cell lines for mRNA expression, homozygous deletion, mutation, and promoter methylation of the p14(ARF) gene. No mRNA expression was detected in 5 of the 7 diffuse-type cell lines. All intestinal cell lines displayed normal levels of expression except for one with a low level of expression. Of the 5 cell lines without expression, 3 (MKN45, NUGC-2, and NUGC-4) and 1 (KATO III) displayed homozygous deletion and methylation of the p14(ARF) gene, respectively. No mutation was found in the whole coding region of the p14(ARF) gene in 8 cell lines without homozygous deletion. Our results indicate that the p14(ARF) gene is more frequently inactivated by homozygous deletion or methylation in diffuse-type gastric cancer cell lines (5/7, 71.4%) than in intestinal ones (0/4, P = 0.022). When we also analyzed 62 primary gastric cancers for the methylation status of the p14(ARF) promoter region, the methylation frequency tended to be higher in diffuse-type gastric cancers (15/33, 45.5%) than in intestinal ones (7/28, 25%). Thus, p14(ARF) alterations might be involved in diffuse-type gastric carcinogenesis.
Volume 87(5)
Pages 654-8
Published 2000-9-1
DOI 10.1002/1097-0215(20000901)87:5<654::aid-ijc6>3.0.co;2-p
PII 10.1002/1097-0215(20000901)87:5<654::AID-IJC6>3.0.CO;2-P
PMID 10925358
MeSH Carrier Proteins / genetics Cyclin-Dependent Kinase Inhibitor p16 DNA Methylation* Gene Deletion Gene Expression Homozygote Humans Immunohistochemistry Mutation Promoter Regions, Genetic / physiology Protein Biosynthesis Proteins / genetics* RNA, Messenger / biosynthesis RNA, Messenger / genetics Reverse Transcriptase Polymerase Chain Reaction Stomach Neoplasms / genetics* Tumor Cells, Cultured Tumor Suppressor Protein p14ARF Tumor Suppressor Protein p53 / biosynthesis Tumor Suppressor Protein p53 / genetics
IF 5.145
Human and Animal Cells GCIY(RCB0555) TGBC11TKB(RCB1148)