Insulin-like growth factor-II gene expression in Wilms' tumour and embryonic tissues

Abstract

Wilms' tumour (nephroblastoma) is an embryonal neoplasm occurring in hereditary and spontaneous forms. Both types show rearrangements of the short arm of chromosome 11. The germ line of children with the rare inherited triad of aniridia, genito-urinary abnormality and mental retardation carry a chromosome 11 that has a deletion in its short arm (band 11p13) and these children are at increased risk of developing Wilms' tumour. Neonates with the Beckwith-Wiedemann syndrome, in which there may be duplication of the 11p13-11p15 region, are similarly predisposed. In the spontaneous form of the tumour a deletion of the 11p14 band in tumour cells, but not in normal cells, has been reported, and the development of homozygosity for recessive mutations in the 11p region is implicated in the aetiology of Wilms' tumour. In view of these chromosomal rearrangements and because Wilms' tumour is histologically indistinguishable from the early stages of kidney development, we have now examined the expression of genes localized to 11p in Wilms' tumour and human embryonic tissue. In 12 sporadic tumours examined, the expression of the gene coding for insulin-like growth factor-II (IGF-II), localized to the 11p15 region, was markedly increased relative to adult tissues, but was comparable to the level of expression in several fetal tissues including kidney, liver, adrenals and striated muscle. This may reflect the stage of tumour differentiation, but could also contribute to the malignant process, as IGF-II is an embryonal mitogen.

Aberrant imprinting of the insulin-like growth factor II receptor gene in Wilms' tumor

“…It is usually diagnosed in the ®rst 5 years of life. At the time of resection, these tumors express IGF2 at levels characteristic of fetal tissues, which are much higher than those found in the surrounding normal kidney (Reeve et al, 1985;Scott et al, 1985). This overexpression may, at least in part, be related to disruption of the parental genomic imprinting of the IGF2 gene.…”

AP-2 may contribute to IGF-II overexpression in rhabdomyosarcoma

“…There are four promoters in the IGF-II gene designated as P1 ± P4. The fetally active P3 promoter leads to expression of a 6.0 kb transcript, which has also been detected in a wide variety of tumors including rhabdomyosarcoma (RMS), a mesenchymal tumor of skeletal muscle origin (Rogler et al, 1994;Scott et al, 1985;Minniti et al, 1994). As a mitogen, IGF-II potently stimulates cell proliferation in human tumors through an autocrine or paracrine manner (EI-Badry et al, 1989;Daughaday, 1990).…”

Sequences of liver cDNAs encoding two different mouse insulin-like growth factor I precursors

“…Nor did the human preproICF-II cDNA probe hybridize to any RNA species on a Northern blot of mouse liver poly(A)+ RNA. Thus, in contrast to adult human or Rhesus monkey liver (13,21,22, L.B.R. unpublished), little if any preproIGF-II mRNA accumulates in adult mouse liver.…”