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. 1999 May;44(5):704–708. doi: 10.1136/gut.44.5.704

Expression of the insulin-like growth factors and their receptors in adenocarcinoma of the colon

S Freier 1, O Weiss 1, M Eran 1, A Flyvbjerg 1, R Dahan 1, I Nephesh 1, T Safra 1, E Shiloni 1, I Raz 1
PMCID: PMC1727486  PMID: 10205209

Abstract

AIMS—To study changes in the expression of insulin-like growth factors (IGFs) and their receptors, as well as production of the IGF-I and IGF-II polypeptides, in adenocarcinoma of the colon. 
METHODS—Malignant tissue obtained at operation was used. Total RNA was extracted and specific IGF-I and IGF-II and their receptor mRNAs were measured by a solution hybridisation RNase protection assay. IGF-I and IGF-II polypeptides were measured by specific immunoassays. 
RESULTS—All normal tissues expressed IGF-II, IGF-I receptor, and IGF-II/mannose-6-phosphate (Man-6-P) receptor. IGF-I mRNA could not be detected but the polypeptide was present in small but equal amounts in normal and malignant tissue. IGF-II was expressed 40 times more abundantly in colonic tumours than in adjacent normal tissue and the concentration of the corresponding polypeptide was twice as high in the malignant tissue. IGF-I receptor expression was increased by a factor of 2.5 and IGF-II/Man-6-P receptor by a factor of 4. 
CONCLUSIONS—This study confirms that in adenocarcinoma of the human colon there is increased expression of IGF-I receptor and IGF-II. Furthermore, IGF-II/Man-6-P receptor message is increased and the increase in IGF-II message is accompanied by a doubling of the IGF-II protein in the tumour tissue compared with the adjacent normal tissue. These findings suggest that the IGF-II/Man-6-P receptor may also be involved in development of adenocarcinoma of the colon. There is rapidly accumulating evidence implicating the IGF system in the development of malignancy of the large bowel. 



Keywords: insulin-like growth factors; adenocarcinoma; colon

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Figure 1 .

Figure 1

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Expression of insulin-like growth factor II (IGF-II)/mannose-6-phosphate (Man-6-P) receptor in colonic tissue. (A) Levels of IGF-II/Man-6-P receptor mRNA in various groups of individuals are compared. The first two lanes are from two healthy individuals (N) followed by two lanes from one patient with a malignant polyp (POL). The next four lanes are from one patient with colonic cancer. The first two are from normal tissue adjacent to the carcinoma (Adj-CRC) and the last two from the tumour itself (CRC). − denotes yeast RNA and probe without RNase, and + denotes yeast RNA and probe with RNase; P denotes native probe. The levels of the IGF-II/Man-6-P receptor mRNA were measured by solution hybridisation RNase protection assay as described in Methods. The gels were exposed for five days. (B) Expression of IGF-II/Man-6-P receptor (IGF-IIR) mRNA in 10 specimens obtained from 10 healthy individuals (N), in four specimens from three patients with a malignant polyp (POL), in nine specimens from six individuals of tissue adjacent to adenocarcinoma (Adj-CRC), and malignant tissue from the same six individuals (CRC). There was a highly significant difference between adenocarcinoma of the colon and the other groups (***p<0.001). mRNA levels were measured by solution hybridisation RNase protection assay as described in Methods. The values are the relative density of the bands as a percentage of the normal tissue. Results are mean (SEM). (C) The integrity of the RNA from these individuals was assessed by visual inspection of ethidium bromide stained 28S and 18S ribosomal bands after agarose gel electrophoresis of 10 µg aliquots. 


Figure 2 .

Figure 2

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Expression of insulin-like growth factor-II (IGF-II) mRNA in adenocarcinoma of the colon (CRC) compared with that in tissue adjacent to the carcinoma (Adj-CRC). mRNA levels were measured by solution hybridisation RNase protection assay as described in Methods. The values are the relative density of the bands as percentage of the normal adjacent tissue coming from six individuals and specimens of adenocarcinoma obtained from the same individuals. There was a highly significant difference (***p<0.001) between the two groups. Results are mean (SEM). 


Figure 3 .

Figure 3

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Expression of insulin-like growth factor-I receptor (IGF-IR) mRNA in adenocarcinoma of the colon (CRC) compared with that in tissue adjacent to the carcinoma (Adj-CRC). mRNA levels were measured by solution hybridisation RNase protection assay as described in Methods. The values are the relative density of the bands as percentage of the normal adjacent tissue consisting of 12 specimens from six individuals and 12 specimens of tissue from the adenocarcinoma obtained from the same six individuals. Results are mean (SEM). There was a highly significant difference (*p<0.0001) between the two groups. 


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