Overexpression of the human insulinlike growth factor I receptor promotes ligand-dependent neoplastic transformation.
The human insulinlike growth factor I receptor was overexpressed in NIH 3T3 cells as well as human and rat primary fibroblast strains. The NIH 3T3 cells displayed a ligand-dependent, highly transformed phenotype. When exposed to insulinlike growth factor I or supraphysiologic levels of insulin, NIH 3T3 cells that expressed high levels of receptors formed aggregates in tissue culture dishes, colonies in soft agar, and tumors in nude mice. Expression of 1 million receptors per cell, a 40-fold increase above the base-line level, was required for anchorage-independent growth. Primary fibroblasts that expressed high levels of receptors displayed a ligand-dependent change in morphology and an increase in saturation density but did not acquire a fully transformed phenotype. The results demonstrate that when amplified, this ubiquitous growth factor receptor behaves like an oncogenic protein and is capable of promoting neoplastic growth in vivo.
Kaleko
M
M
Program in Molecular Medicine, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Rutter
W J
WJ
Miller
A D
AD
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D005796:Genes; D005822:Genetic Vectors; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D008024:Ligands; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000378:metabolism*; D014162:Transfection
D007328:Insulin; D008024:Ligands; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I