Overexpression of the human insulinlike growth factor I receptor promotes ligand-dependent neoplastic transformation.

Publication Type:

Journal Article

Source:

Molecular and cellular biology, Volume 10, Issue 2, p.464-73 (1990)

Keywords:

1990, Animals, Cell Division, Cell Line, Cell Transformation, Neoplastic, Cells, Cultured, Flow Cytometry Core Facility, Fluorescent Antibody Technique, gene expression, GENES, Genetic Vectors, Humans, Insulin, Insulin-Like Growth Factor I, Kinetics, Ligands, MICE, Mice, Inbred Strains, PHENOTYPE, Rats, Receptors, Cell Surface, Receptors, Somatomedin, Somatomedins, Transfection

Abstract:

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.