IGF-II in primary human colorectal tumors: Peptide level, activated promoters, parental imprinting and gene rearrangement

IGF-II is a polypeptide growth factor with growth and differentiation promo ting activities, involved in human development. We have reported previously ICF-II mRNA and peptide overexpression in primary human colon cancers. Her e we show that the IGF-II peptide content is increased in six primary colon cancers compared to the corresponding healthy tissues. The IGF-II transcri pts in healthy and cancerous colon tissues were identified by Northern blot ting and RT-PCR. Promoters P3 and P4 were active in most tissues. Relaxatio n of parental imprinting was observed in two tumors and one healthy tissue, without any correlation with the ICF-II transcript levels. Rearrangements of the IGF-II gene in two tumors containing very high amounts of ICF-II mRN A are described. Fragments containing the breakpoints were cloned by the ve ctorette-PCR strategy. In both tumors, the breakpoints occurred in repetiti ve sequences. In one tumor (T11), the breakpoint was localized 2 kb downstr eam the end of exon 9. The second tumor (T18) contains two modified alleles . In one rearranged allele the breakpoint is located in exon 9. The exact p osition of the breakpoint in the second rearranged allele has not been iden tified. In future experiments, the correlation between the gene rearrangeme nts and ICF-II mRNA overexpression will be studied.