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Diehl, D.* ; Hessel, E.* ; Oesterle, D. ; Renner-Müller, I.* ; Elmlinger, M.* ; Langhammer, M.* ; Göttlicher, M. ; Wolf, E.* ; Lahm, H.* ; Hoeflich, A.*

IGFBP-2 overexpression reduces the appearance of dysplastic aberrant crypt foci and inhibits growth of adenomas in chemically induced colorectal carcinogenesis.

Int. J. Cancer 124, 2220-2225 (2009)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords IGFBP-2; growth inhibition; ACF; colon cancer; 1;2-dimethylhydrazine; factor-binding protein-2; serum c-peptide; colon carcinogenesis; transgenic mice; rectal-cancer; factor-i; risk; nutrition; tumorigenesis; epidemiology
ISSN (print) / ISBN 0020-7136
e-ISSN 1097-0215
Journal International Journal of Cancer
Quellenangaben Volume: 124, Issue: 9, Pages: 2220-2225 Article Number: , Supplement: ,
Publisher Wiley
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Toxicology and Pharmacology (TOX)