{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T02:28:04Z","timestamp":1768876084501,"version":"3.49.0"},"reference-count":42,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2013,5,25]],"date-time":"2013-05-25T00:00:00Z","timestamp":1369440000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:p>The growth arrest DNA damage\u2010inducible gene (GADD45) family, which is composed of GADD45A, GADD45B, and GADD45G, may play similar but not identical roles in tumorigenesis. Genetic changes associated with or responsible for their dysregulation are in general uncommon. This study was to detect the role of GADD45 gene family in gastric cardia adenocarcinoma (GCA) and the relationship of GADD45A and GADD45G methylation to a series of pathological parameters in a large GCA sample, in order to elucidate more information on the role of GADD45 gene family with regard to the pathogenesis of GCA. Decreased mRNA and protein expression of GADD45A and GADD45G but not GADD45B were found in 138 GCA tumor tissues. The methylation frequency of 5\u2032 4 CpG region located in distal promoter of GADD45A and proximal promoter of GADD45G in GCA tumor tissues was significantly higher than that in corresponding normal tissues. The expression levels of GADD45A and GADD45G were inversely correlated with methylation levels. GADD45B expression was not correlated with GCA patients survival, while GADD45A and GADD45G methylation status and protein expression were independently associated with GCA patients' survival. These results suggest that GADD45A and GADD45G gene may act as functional tumor suppressor but being frequently inactivated epigenetically in patients with GCA. Silencing of GADD45A and GADD45G, negative regulator of cell growth, is most likely responsible for conferring a selective growth advantage during GCA evolution and outgrowth.<\/jats:p>","DOI":"10.1002\/ijc.28223","type":"journal-article","created":{"date-parts":[[2013,4,24]],"date-time":"2013-04-24T15:34:18Z","timestamp":1366817658000},"page":"2043-2053","source":"Crossref","is-referenced-by-count":40,"title":["Methylation\u2010mediated repression of GADD45A and GADD45G expression in gastric cardia adenocarcinoma"],"prefix":"10.1002","volume":"133","author":[{"given":"Wei","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Pathology, Hebei Cancer Institute the Fourth Hospital of Hebei Medical University Shijiazhuang Hebei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiming","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hebei Cancer Institute the Fourth Hospital of Hebei Medical University Shijiazhuang Hebei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanli","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hebei Cancer Institute the Fourth Hospital of Hebei Medical University Shijiazhuang Hebei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhifeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hebei Cancer Institute the Fourth Hospital of Hebei Medical University Shijiazhuang Hebei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Kuang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hebei Cancer Institute the Fourth Hospital of Hebei Medical University Shijiazhuang Hebei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhibin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hebei Cancer Institute the Fourth Hospital of Hebei Medical University Shijiazhuang Hebei China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,5,25]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v12.i1.17"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djs003"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/156652412800619978"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05515"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.9.10.4196"},{"key":"e_1_2_6_7_1","first-page":"268","article-title":"Stress sensor Gadd45 genes as therapeutic targets in cancer","volume":"7","author":"Cretu A","year":"2009","journal-title":"Cancer Ther"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevOncog.v16.i1-2.120"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307869200"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2184.2000.00187.x"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-009-0516-9"},{"key":"e_1_2_6_12_1","first-page":"2563","article-title":"Clinicopathological significance of abnormalities in Gadd45 expression and its relationship to p53 in human pancreatic cancer","volume":"8","author":"Yamasawa K","year":"2002","journal-title":"Clin Cancer Res"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-0267"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10059-010-0092-1"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-3609"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63425-6"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207193"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208464"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-022031"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-010-0777-z"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.87.3.1262"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2168.1998.00940.x"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1054\/bjoc.2001.2034"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/07357900802620828"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2003.08.005"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/18.11.1427"},{"key":"e_1_2_6_27_1","first-page":"235","article-title":"The CpG island searcher: a new WWW resource","volume":"3","author":"Takai D","year":"2003","journal-title":"In Silico Biol"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(99)01971-X"},{"key":"e_1_2_6_29_1","first-page":"338S\u20109S","article-title":"Vitamin nutrition and gastroesophageal cancer","volume":"130","author":"Yang CS.","year":"2000","journal-title":"J Nutr"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgh247"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10552-006-0097-4"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0b013e3180f6262c"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2011.04.006"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10585-012-9533-x"},{"key":"e_1_2_6_35_1","first-page":"2143","article-title":"Down\u2010regulation of Gadd45 expression is associated with tumor differentiation in non\u2010small cell lung cancer","volume":"26","author":"Higashi H","year":"2006","journal-title":"Anticancer Res"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-9966-31-11"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.21637"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4821"},{"key":"e_1_2_6_39_1","first-page":"2579","article-title":"The differentiation primary response gene MyD118, related to GADD45,encodes for a nuclear protein which interacts with PCNA and p21WAF1\/CIP1","volume":"12","author":"Vairapandi M","year":"1996","journal-title":"Oncogene"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202885"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64329-5"},{"key":"e_1_2_6_42_1","first-page":"3783","article-title":"A sequential treatment of depsipeptide followed by 5\u2010azacytidine enhances Gadd45beta expression in hepatocellular carcinoma cells","volume":"27","author":"Jiang C","year":"2007","journal-title":"Anticancer Res"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0706550"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.28223","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.28223","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T18:36:04Z","timestamp":1696358164000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.28223"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5,25]]},"references-count":42,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2013,11]]}},"alternative-id":["10.1002\/ijc.28223"],"URL":"https:\/\/doi.org\/10.1002\/ijc.28223","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5,25]]}}}