Insulin-like growth factor binding protein-1 over-expression in transgenic mice inhibits hepatic preneoplasia

• Published in: Molecular carcinogenesis 2003-03, Vol.36 (3), p.142-146
• Main Authors: Lu, Suying, Archer, Michael C.
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Body Weight - drug effects; Carcinogens; Diethylnitrosamine; Gene Expression Regulation; hepatic preneoplasia; hepatocarcinogenesis; Humans; Insulin-Like Growth Factor Binding Protein 1 - genetics; Insulin-Like Growth Factor Binding Protein 1 - metabolism; insulin-like growth factor binding protein-1 (IGFBP-1); Liver - drug effects; Liver - metabolism; Liver - pathology; Liver - physiology; Liver Neoplasms - chemically induced; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Male; Metallothionein - genetics; Mice; Mice, Inbred C57BL; Mice, Transgenic; Organ Size - drug effects; Precancerous Conditions - genetics; Precancerous Conditions - pathology; Promoter Regions, Genetic; transgenic mice; Zinc - pharmacology
• ISSN: 0899-1987; 1098-2744
• DOI: 10.1002/mc.10105

Insulin‐like growth factor binding protein‐1 (IGFBP‐1) is synthesized in the liver and regulates the mitogenic effects of the insulin‐like growth factors (IGFs). The evidence that IGFBP‐1 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 IGFBP‐1 gene is under the control of the mouse metallothionein promoter. The lesions were induced by treating 15‐d‐old 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‐type mice treated with zinc (36.4% versus 85.7% and 83.3%, respectively, P