title: Tumour suppression associated with expression of human insulin-like growth factor II.
abstract: Recent circumstantial evidence has implicated Insulin-like growth factor II in the genesis of several tumour types, notably developmental tumours (Scott et al., 1985; Schofield & Tate, 1987; Wilkins et al., 1989). This type of tumour, thought to originate during the defective differentiation of organ precursors (Miereau et al., 1987), often expresses greatly elevated levels of mRNA for IGF-II, a known mitogen for these cells and abundantly expressed in their presumed normal counterparts (Scott et al., 1985; Schofield & Tate, 1987; Gray et al., 1987). It has been proposed that continued, inappropriate expression of this gene drives tumour growth by an autocrine mechanism. In order to examine the potential role of IGF-II in the growth of tumour cells an IGF-II cDNA was introduced into a retroviral expression vector, and used to infect a cloned fibroblast cell line. Expression of IGF-II conferred a degree of serum independence of growth in cell culture, however, when cells were injected into nude mice as subcutaneous grafts, clones expressing IGF-II from the retrovirus were found to have a greatly increased (five fold) latency of sarcoma formation. After a prolonged lag all cell lines eventually gave rise to tumours in which the introduced IGF-II genes had either been lost or inactivated, suggesting that in this system IGF-II acts as a tumour suppressor gene.
authors.affiliation: Department of Zoology, University of Oxford, UK.
authors.forename: P N
authors.initials: PN
authors.lastname: Schofield
authors.forename: A
authors.initials: A
authors.lastname: Lee
authors.forename: D J
authors.initials: DJ
authors.lastname: Hill
authors.forename: J E
authors.initials: JE
authors.lastname: Cheetham
authors.forename: D
authors.initials: D
authors.lastname: James
authors.forename: C
authors.initials: C
authors.lastname: Stewart
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D005347:Fibroblasts / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000493:pharmacokinetics; D051379:Mice; D008808:Mice, Inbred CBA; D008819:Mice, Nude; D014162:Transfection
chemical_list: D007335:Insulin-Like Growth Factor II