{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:41:49Z","timestamp":1790869309440,"version":"4.1.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":2861,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"Public Health Service Grant from the National Institute of Diabetes and Digestive and Kidney Diseases","award":["DK-59866"],"award-info":[{"award-number":["DK-59866"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,11]]},"abstract":"\n \n \n The<\/jats:bold>\n \n Glypican 3\n <\/jats:bold>\n (<\/jats:bold>\n \n Gpc3\n <\/jats:bold>\n ) gene is expressed abundantly in the fetal liver, is inactive in the normal adult liver, and is frequently reactivated in hepatocellular carcinoma (HCC). This reactivation in HCC has led to considerable interest in Gpc3 as a diagnostic tumor marker and its possible role in tumorigenesis. Despite this interest, the basis for<\/jats:bold>\n \n Gpc3\n <\/jats:bold>\n regulation is poorly understood. On the basis of the similarities between<\/jats:bold>\n \n Gpc3\n <\/jats:bold>\n and<\/jats:bold>\n \n alpha\n <\/jats:bold>-\n fetoprotein\n <\/jats:bold>\n expression in the liver, we reasoned that common factors might regulate these 2 genes. Here we identify zinc fingers and homeoboxes 2 (Zhx2) as a regulator of<\/jats:bold>\n \n Gpc3\n <\/jats:bold>\n . Mouse strain\u2013specific differences in adult liver<\/jats:bold>\n \n Gpc3\n <\/jats:bold>\n messenger RNA levels and transgenic mouse studies indicate that Zhx2 represses Gpc3 expression in the adult liver. We also demonstrate that<\/jats:bold>\n \n Gpc3\n <\/jats:bold>\n is activated in the regenerating liver following a carbon tetrachloride treatment and that the level of<\/jats:bold>\n \n Gpc3\n <\/jats:bold>\n induction is controlled by alpha-fetoprotein regulator 2 (Afr2).<\/jats:bold>\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n \n We show that Zhx2 acts as a repressor of<\/jats:bold>\n \n Gpc3\n <\/jats:bold>\n in the adult liver, and this raises the interesting possibility that Zhx2 might also be involved in<\/jats:bold>\n \n Gpc3\n <\/jats:bold>\n reactivation in HCC. We also show that<\/jats:bold>\n \n Gpc3\n <\/jats:bold>\n is activated in the regenerating liver in an Afr2-dependent manner. Zhx2 and Afr2 represent the first known regulators of<\/jats:bold>\n \n Gpc3\n <\/jats:bold>\n .<\/jats:bold>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/hep.21825","type":"journal-article","created":{"date-parts":[[2007,8,2]],"date-time":"2007-08-02T01:16:27Z","timestamp":1186017387000},"page":"1541-1547","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":81,"title":["The oncofetal gene glypican 3 is regulated in the postnatal liver by zinc fingers and homeoboxes 2 and in the regenerating liver by alpha-fetoprotein regulator 2"],"prefix":"10.1097","volume":"46","author":[{"given":"Lorri A.","family":"Morford","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneta","family":"Dobierzewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha L.","family":"Peterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett T.","family":"Spear","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-28-20241201","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1006\/scdb.2000.0240","article-title":"Developmental roles of the glypicans.","volume":"12","author":"De 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syndrome.","volume":"12","author":"Pilia","year":"1996","journal-title":"Nat Genet"},{"key":"R6-28-20241201","first-page":"807","article-title":"Frequent silencing of the GPC3 gene in ovarian cancer cell lines.","volume":"59","author":"Lin","year":"1999","journal-title":"Cancer Res"},{"key":"R7-28-20241201","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/sj.onc.1203322","article-title":"Expression of GPC3, an Xlinked recessive overgrowth gene, is silenced in malignant mesothelioma.","volume":"19","author":"Murthy","year":"2000","journal-title":"Oncogene"},{"key":"R8-28-20241201","doi-asserted-by":"crossref","first-page":"7408","DOI":"10.1038\/sj.onc.1204925","article-title":"Glypican3 expression is silenced in human breast cancer.","volume":"20","author":"Xiang","year":"2001","journal-title":"Oncogene"},{"key":"R9-28-20241201","first-page":"5179","article-title":"Cloning and expression of a developmentally regulated transcript MXR7 in hepatocellular carcinoma: 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