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IGFBP‐2 overexpression reduces the appearance of dysplastic aberrant crypt foci and inhibits growth of adenomas in chemically induced colorectal carcinogenesis
Author(s) -
Diehl Daniela,
Hessel Esther,
Oesterle Doris,
RennerMüller Ingrid,
Elmlinger Martin,
Langhammer Martina,
Göttlicher Martin,
Wolf Eckhard,
Lahm Harald,
Hoeflich Andreas
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24193
Subject(s) - aberrant crypt foci , carcinogenesis , colorectal cancer , crypt , genetically modified mouse , 1,2 dimethylhydrazine , transgene , cancer research , endocrinology , cell growth , medicine , adenoma , biology , pathology , cancer , azoxymethane , colonic disease , biochemistry , genetics , gene
Colon cancer patients frequently show increased levels of serum insulin‐like growth factor‐binding protein‐2 (IGFBP‐2), however, the pathogenetic relevance of this phenomenon for colorectal cancer is unclear. Therefore, we have used IGFBP‐2 transgenic animals which overexpress IGFBP‐2 systemically and locally in the intestine to study its role in chemically induced colorectal carcinogenesis. Mice received intraperitoneal injections of 1,2‐dimethylhydrazine (DMH) (40 mg/kg body weight) once a week for 6 weeks to selectively induce aberrant crypt foci (ACF) and tumors in the colon. While tumor incidence was comparable in transgenic and control mice, the volume of adenomas in IGFBP‐2 transgenic mice was reduced more than 2‐fold. Furthermore, serum IGFBP‐2 levels negatively correlated with tumor volume in the IGFBP‐2 transgenic group. Histological examination showed that IGFBP‐2 transgenic mice developed significantly less dysplastic ACF with a high potential to progress to advanced stages. The reduced tumor volume in IGFBP‐2 transgenic animals was due to significantly reduced proliferative capacity, evidenced by a lower proportion of cells positive for Ki67. Our results demonstrate for the first time in an experimental model that IGFBP‐2 overabundance prior to the onset and during colorectal carcinogenesis reduces tumor growth by inhibition of cell proliferation. © 2008 Wiley‐Liss, Inc.