{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:14:11Z","timestamp":1790810051490,"version":"4.1.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Cancer"],"published-print":{"date-parts":[[2005,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Metallothionein 3 (MT3) inhibits growth in a variety of cell types. We measured\n                      <jats:italic>MT3<\/jats:italic>\n                      gene expression by RT-PCR, and DNA methylation in the\n                      <jats:italic>MT3<\/jats:italic>\n                      promoter by combined bisulphite restriction analysis, in four oesophageal cancer cell lines and the resected oesophagus from 64 patients with oesophageal squamous cell carcinoma (SCC).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>MT3<\/jats:italic>\n                      expression was not detected in one of the four oesophageal cell lines. The\n                      <jats:italic>MT3<\/jats:italic>\n                      promoter was methylated in all of the oesophageal cell lines, but the degree of methylation was greater in the non-expressing cell line. After treatment with 5-aza-2'-deoxycytidine there was a reduction in the degree of methylation, and an increase in\n                      <jats:italic>MT3<\/jats:italic>\n                      expression, in each of the cell lines (p &lt; 0.01). Methylation was detected in 52% (33 of 64) of primary SCC and 3% (2 of 62) of histologically normal resection margins.\n                      <jats:italic>MT3<\/jats:italic>\n                      expression was measured in 29 tumours, 17 of which had methylation of\n                      <jats:italic>MT3<\/jats:italic>\n                      . The expression of\n                      <jats:italic>MT3<\/jats:italic>\n                      was significantly less in the methylated tumours compared to either the unmethylated tumours (p = 0.03), or the matched margin (p = 0.0005). There was not a significant difference in\n                      <jats:italic>MT3<\/jats:italic>\n                      expression between the tumour and the margin from patients with unmethylated tumour. No correlations were observed between methylation of\n                      <jats:italic>MT3<\/jats:italic>\n                      and survival time, patient age, gender, smoking or drinking history, tumour stage, volume, or lymph node involvement.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We conclude that\n                      <jats:italic>MT3 ex<\/jats:italic>\n                      pression is frequently down-regulated in oesophageal SCC, by DNA methylation, but that this is not a prognostic indicator.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/1476-4598-4-42","type":"journal-article","created":{"date-parts":[[2005,12,14]],"date-time":"2005-12-14T02:33:00Z","timestamp":1134527580000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Metallothionien 3 expression is frequently down-regulated in oesophageal squamous cell carcinoma by DNA methylation"],"prefix":"10.1186","volume":"4","author":[{"given":"Eric","family":"Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A","family":"Drew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Qing","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neville J","family":"De Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Feng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George C","family":"Mayne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R","family":"Ruszkiewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David I","family":"Watson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glyn G","family":"Jamieson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2005,12,13]]},"reference":[{"key":"131_CR1","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1146\/annurev.bi.55.070186.004405","volume":"55","author":"DH Hamer","year":"1986","unstructured":"Hamer DH: Metallothionein. 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