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Mol Cell Biol. 1990 February; 10(2): 464-473

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

M Kaleko, W J Rutter and A D Miller

Program in Molecular Medicine, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.

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.

Mol Cell Biol. 1990 February; 10(2): 464-473




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