Structural alteration of the insulin-like growth factor II-gene in Wilms tumour

Abstract

In this study messenger ribonucleic acid (mRNA) and DNA of five Wilms tumours were investigated. As expected, the level of insulin-like growth factor (IGF) II-mRNA was elevated up to 50 times in tumour tissue as compared to normal adjacent kidney tissue. In addition, genomic DNA was isolated and digested with appropriate restriction enzymes. Southern blots were prepared and hybridized to IGF II-cDNA probes. Additional bands were present in one of the five Wilms tumours compared to normal tissue. The results indicate a rearrangement of the IGF II-gene on one of the two chromosomes. It is speculated, that this change is responsible for the elevated IGF II expression which may be a factor contributing to tumour growth.

Involvement of IGF-II in human cancer

“…Many Wilms' tumors express very high levels of IGF-II mRNA (Reeve et al 1985, Scott et al 1985, Gansler et al 1988, Irminger et al 1989, Yun et al 1993a, elevated levels of IGF-II protein (Ren-Qiu et al 1993), and overexpress the IGF-I receptor (Gansler et al 1988, Baxter & Daughaday 1991. Wilms' tumor cell lines are growth-inhibited both in vitro and in vivo (nude mice) when treated with IR-3, an IGF-I receptor blocking monoclonal antibody (Korn et al 1995).…”

Growth at the Cellular Level

“…As the IGF-11 gene is closely linked to insulin ( 1.4 kb 3') ( 16) it is a reasonable assumption that the IGF-11 gene is included in these lesions. A reduction of IGF-11 gene dosage or rearrangement has been found in such tumours (17), which would not be expected if selection for autocrine growth occurred in the tumour, based on high levels of expression of bioactive IGF-II. Using xenografts of primary Wilms' tumours it was demonstrated that selection against IGF-11 expression occurred during tumour passage, and elevated IGF-11 mRNA appeared not to be an essential component of tumour progression (18).…”

The Regulation of Growth by Insulinlike Growth FactorII

“…These included five adenocarcinomas and two adenomas. Furthermore, enhanced expression of the IGF-II gene has been implicated in the pathogenesis of Wilms' tumor (169,186,299) and several other tumors. These include adrenocorticocarcinomas (280), rhabdomyosarcomas (112,207,355), non-islet cell tumor hypoglycemia (83,227), pheochromocytomas (113), neuroblastomas (113), and hepatoblastomas, all of which appear to secrete large amounts of IGF-II (39, 280, 355).…”