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


METHODS
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.
Vrieling
Alina
A
Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Voskuil
Dorien W
DW
Bosma
Astrid
A
Majoor
Donné M
DM
van Doorn
Jaap
J
Cats
Annemieke
A
Depla
Annekatrien C T M
AC
Timmer
Robin
R
Witteman
Ben J M
BJ
Wesseling
Jelle
J
Kampman
Ellen
E
Van't Veer
Laura J
LJ
D000328:Adult; D000368:Aged; D003106:Colon / Q000378:metabolism*; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis*; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis*; D017527:Receptor, IGF Type 2 / Q000096:biosynthesis*; D012007:Rectum / Q000378:metabolism*; D044967:Serum
D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D017527:Receptor, IGF Type 2; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1