Expression of insulin-like growth factor system components in colorectal tissue and its relation with serum IGF levels

CONTEXT:

The insulin-like growth factor (IGF)-system has been implicated in colorectal tumor carcinogenesis. Although both tumor expression levels and serum concentrations of IGF-system components are related to colorectal cancer risk, it is unknown whether IGF levels in tissue and serum are correlated.

OBJECTIVE:

The objective of this study was to determine expression levels of various IGF-system components in different locations of the colorectum, and to investigate whether normal tissue IGF expression levels are correlated with serum IGF-I and IGF-II concentrations.

DESIGN:

Biopsies from macroscopically normal mucosa at four locations in the colorectum (ascending, transverse, sigmoid colon, and rectum) and a fasting serum sample were obtained from 48 asymptomatic patients at increased risk of colorectal cancer. Expression levels of IGF-I, IGF-II, IGF-IR, IGF-IIR, and IGFBP-3 messenger RNA (mRNA) in tissue were quantitatively evaluated using real-time RT-PCR. Expression of IGF-IR protein in the ascending colon and rectum tissue specimens was assessed semi-quantitatively by immunohistochemistry. Serum IGF-I and IGF-II concentrations were determined using immunometric assays.

RESULTS:

With the exception of IGF-IIR, mRNA levels of all the IGF-system components investigated, as well as IGF-IR protein expression, were significantly higher in the rectum compared with the ascending colon (p<or=0.001). Serum IGF-I and IGF-II concentrations did not correlate with any of the parameters studied in colorectal tissues.

CONCLUSIONS:

Our results indicate that in humans IGF-system components are differentially expressed in the colorectum. Moreover, our findings suggest that local and circulating components of the IGF-system are differentially regulated. However, due to large intra-individual variation in mRNA expression, we cannot formally exclude undetected but existing routes of co-regulation.

Authors: 
A. Vrieling, D.W. Voskuil, A. Bosma, D.M. Majoor, J. van Doorn, A. Cats, A.C. Depla, R. Timmer, B.J. Witteman, J. Wesseling, E. Kampman, L.J. van 't Veer
DOI: 
10.1016/j.ghir.2008.08.004
Pages: 
2009; 19 (2): 126-135
Published in: 
Growth Hormone & IGF Research
Date of publication: 
April, 2009
Status of the publication: 
Published/accepted