{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:12:33Z","timestamp":1791119553863,"version":"4.1.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"5","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1994,3]]},"abstract":"<jats:p>Reduced expression of E-cadherin has been regarded\nas one of the main molecular events involved in dysfunction of the cell-cell\nadhesion system, triggering cancer invasion and metastasis. However, even with a\nsufficient amount of E-cadherin, cell-cell adhesion is sometimes lost in\n\"diffusely invasive\" human carcinomas. Ten human cancer cell lines,\nshowing growth characterized morphologically by loose cell-cell adhesion, were\nanalyzed for possible structural abnormalities of their expressed E-cadherin.\nFour of the cell lines showed strong mRNA and protein expression with no\nnucleotide sequence abnormalities, and mRNA was absent in four other cell lines.\nmRNA sequence was abnormal in the remaining two gastric carcinoma cell lines. In\nMKN45 (poorly differentiated adenocarcinoma), this involved a 12-bp in-frame\ndeletion with strong expression of mRNA and protein. In KATO-III (signet ring\ncell carcinoma), there were four mRNA species with insertions of different\nsizes, among which the major transcripts (with a 7-bp insertion) caused a\nframeshift, and expression of both mRNA and protein was markedly reduced. In\nthese two cell lines, DNA mutations were detected around exon-intron junctions,\nrevealing that aberrant RNA splicing was the cause of the mRNA abnormalities. In\naddition, the wild-type allele of the E-cadherin locus was lost, suggesting that\nthe E-cadherin gene had been inactivated by two hits (mutation and allele loss),\nsimilar to the mechanism for inactivation of tumor suppressor\ngenes.<\/jats:p>","DOI":"10.1073\/pnas.91.5.1858","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T09:05:56Z","timestamp":1149066356000},"page":"1858-1862","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":225,"title":["E-cadherin gene mutations in human gastric carcinomacell lines."],"prefix":"10.1073","volume":"91","author":[{"given":"T","family":"Oda","sequence":"first","affiliation":[{"name":"Pathology Division, National Cancer Center Research\rInstitute, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Kanai","sequence":"additional","affiliation":[{"name":"Pathology Division, National Cancer Center Research\rInstitute, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Oyama","sequence":"additional","affiliation":[{"name":"Pathology Division, National Cancer Center Research\rInstitute, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Yoshiura","sequence":"additional","affiliation":[{"name":"Pathology Division, National Cancer Center Research\rInstitute, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Shimoyama","sequence":"additional","affiliation":[{"name":"Pathology Division, National Cancer Center Research\rInstitute, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"Birchmeier","sequence":"additional","affiliation":[{"name":"Pathology Division, National Cancer Center Research\rInstitute, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Sugimura","sequence":"additional","affiliation":[{"name":"Pathology Division, National Cancer Center Research\rInstitute, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Hirohashi","sequence":"additional","affiliation":[{"name":"Pathology Division, National Cancer Center Research\rInstitute, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1994,3]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.91.5.1858","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T14:03:52Z","timestamp":1649858632000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.91.5.1858"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,3]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1994,3]]}},"alternative-id":["10.1073\/pnas.91.5.1858"],"URL":"https:\/\/doi.org\/10.1073\/pnas.91.5.1858","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,3]]},"assertion":[{"value":"1994-03-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}