E-cadherin gene mutations in human gastric carcinoma\ncell lines.

来自 NCBI

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作者：

T Oda，Y Kanai，T Oyama，K Yoshiura，Y Shimoyama，W Birchmeier，T Sugimura，S Hirohashi

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摘要：

Reduced expression of E-cadherin has been regardedas one of the main molecular events involved in dysfunction of the cell-celladhesion system, triggering cancer invasion and metastasis. However, even with asufficient amount of E-cadherin, cell-cell adhesion is sometimes lost in"diffusely invasive" human carcinomas. Ten human cancer cell lines,showing growth characterized morphologically by loose cell-cell adhesion, wereanalyzed for possible structural abnormalities of their expressed E-cadherin.Four of the cell lines showed strong mRNA and protein expression with nonucleotide sequence abnormalities, and mRNA was absent in four other cell lines.mRNA sequence was abnormal in the remaining two gastric carcinoma cell lines. InMKN45 (poorly differentiated adenocarcinoma), this involved a 12-bp in-framedeletion with strong expression of mRNA and protein. In KATO-III (signet ringcell carcinoma), there were four mRNA species with insertions of differentsizes, among which the major transcripts (with a 7-bp insertion) caused aframeshift, and expression of both mRNA and protein was markedly reduced. Inthese two cell lines, DNA mutations were detected around exon-intron junctions,revealing that aberrant RNA splicing was the cause of the mRNA abnormalities. Inaddition, the wild-type allele of the E-cadherin locus was lost, suggesting thatthe E-cadherin gene had been inactivated by two hits (mutation and allele loss),similar to the mechanism for inactivation of tumor suppressorgenes.

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关键词：

Medical Sciences Cancer Invasion and Metastasis Cell-Cell Adhesion Aberrant RNA Splicing

DOI：

10.1073/pnas.91.5.1858

被引量：

663

年份：

1994