Overexpression of the insulin-like growth factor I receptor in @entity1 XXXX .

@entity1 @entity3208 @entity5 @entity442 @entity3909 @entity5100 @entity2975 @entity14 @entity2856 @entity694
BACKGROUND: High concentrations of @entity442 and @entity5100 have been demonstrated in @entity1 @entity694 and exert mitogenic effects through paracrine/autocrine interactions with the @entity2856 ( @entity2856 ). However, definitive studies of @entity2856 expression in these tissues have not been performed. METHODS: To study changes in the levels of the @entity2856 in @entity14 , we analyzed the expression of @entity2856 in 40 paired samples of normal and @entity3909 colonic tissue by quantitative reverse-transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and ligand binding. RESULTS: As measured by RT-PCR, the @entity2856 mRNA ratio in paired @entity5 and adjacent normal mucosa was higher than 2.0 in 32 of 40 (80%) samples. The overall mean @entity2856 mRNA level was five-fold higher in @entity5 versus adjacent normal mucosa (P < 0.0001). Overexpression of @entity2856 in @entity694 was confirmed at the protein level by immunohistochemistry and receptor-binding studies. @entity694 cells exhibited a positive staining for @entity2856 in 91% of all @entity5 (30 of 33) whereas the adjacent normal colonic epithelial cells showed only a very faint or no significant @entity2856 immunoreactivity. Radioligand assays and Scatchard analysis in both tissue types revealed a single class of high-affinity @entity2856 -binding sites with a similar dissociation constant (K(d;) 0.14 +/- 0.02 nmol/L, n = 18). However, specific (125) @entity442 -binding and receptor concentrations were elevated in @entity5 membranes compared with normal mucosa (33.6 +/- 5.6 vs. 22.7 +/- 3.4 fmol/mg protein, P < 0.05). @entity442 affinity crosslinking and @entity3208 - @entity2975 gel electrophoresis displayed specific bands corresponding to the size of the normal alpha-subunit of the @entity2856 that were more intense in @entity3909 samples. @entity5100 mRNA levels were significantly elevated in @entity14 (P < 0.0001). The @entity5100 mRNA ratio in @entity5 versus normal tissue was elevated more than twofold in 28 of 40 paired samples and a positive correlation was observed between the overexpression of @entity5100 and @entity2856 in the @entity5 . CONCLUSIONS: Our results demonstrate that, in addition to @entity5100 , a strong overexpression of @entity2856 is found in the majority of @entity14 , supporting the hypothesis of an important role of the IGF system in the pathogenesis of @entity14 .
