{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T14:40:43Z","timestamp":1761057643358},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2003,2,27]],"date-time":"2003-02-27T00:00:00Z","timestamp":1046304000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2003,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Insulin\u2010like growth factor binding protein\u20101 (IGFBP\u20101) is synthesized in the liver and regulates the mitogenic effects of the insulin\u2010like growth factors (IGFs). The evidence that IGFBP\u20101 plays a role in hepatocarcinogenesis, however, is equivocal. We have, therefore, investigated the development of preneoplastic hepatic lesions in transgenic mice in which the human <jats:italic>IGFBP\u20101<\/jats:italic> gene is under the control of the mouse metallothionein promoter. The lesions were induced by treating 15\u2010d\u2010old male mice with a single intraperitoneal injection of 5 mg\/kg diethylnitrosamine (DENA). Lesions were scored when the mice were 28 wk of age. Quantitative microscopy of liver sections revealed that significantly fewer transgenic mice treated with zinc to activate the transgene had focal lesions compared to either transgenic mice not treated with zinc or wild\u2010type mice treated with zinc (36.4% versus 85.7% and 83.3%, respectively, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05 in each case). Zinc\u2010treated transgenic mice also had significantly fewer lesions per liver (11.5\u2009\u00b1\u20095.0 versus 74.7\u2009\u00b1\u200918.4 and 59.4\u2009\u00b1\u200915.6, respectively, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01 in each case) and a smaller percentage of liver volume occupied by lesions (0.2\u2009\u00b1\u20090.1 versus 1.4\u2009\u00b1\u20090.3 and 1.1\u2009\u00b1\u20090.4 respectively, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05 in each case). Immunohistochemical staining showed that both IGF\u2010I and IGF\u2010II were overexpressed in most of the lesions. These results show that expression of the <jats:italic>IGFBP\u20101<\/jats:italic> transgene leads to a marked inhibition of hepatic preneoplasia, possibly by decreasing the mitogenic activity of IGF\u2010I and\/or IGF\u2010II. This study adds new evidence to the notion that the IGF axis plays an important role in liver cancer development. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mc.10105","type":"journal-article","created":{"date-parts":[[2003,3,18]],"date-time":"2003-03-18T22:55:41Z","timestamp":1048028141000},"page":"142-146","source":"Crossref","is-referenced-by-count":16,"title":["Insulin\u2010like growth factor binding protein\u20101 over\u2010expression in transgenic mice inhibits hepatic preneoplasia"],"prefix":"10.1002","volume":"36","author":[{"given":"Suying","family":"Lu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael 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