title: Expression of insulin-like growth factor system components in colorectal tissue and its relation with serum IGF levels.
abstract: 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.
authors.affiliation: Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Alina
authors.initials: A
authors.lastname: Vrieling
authors.forename: Dorien W
authors.initials: DW
authors.lastname: Voskuil
authors.forename: Astrid
authors.initials: A
authors.lastname: Bosma
authors.forename: Donné M
authors.initials: DM
authors.lastname: Majoor
authors.forename: Jaap
authors.initials: J
authors.lastname: van Doorn
authors.forename: Annemieke
authors.initials: A
authors.lastname: Cats
authors.forename: Annekatrien C T M
authors.initials: AC
authors.lastname: Depla
authors.forename: Robin
authors.initials: R
authors.lastname: Timmer
authors.forename: Ben J M
authors.initials: BJ
authors.lastname: Witteman
authors.forename: Jelle
authors.initials: J
authors.lastname: Wesseling
authors.forename: Ellen
authors.initials: E
authors.lastname: Kampman
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Van't Veer
mesh_terms: 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
chemical_list: 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