Clinical Cancer Research, Vol 2, Issue 12 2037-2042, Copyright © 1996 by American Association for Cancer Research

ARTICLES

Regulation of insulin-like growth factor I receptor expression by the pure antiestrogen ICI 182780

H Huynh, T Nickerson, M Pollak and X Yang
Lady Davis Research Institute, and Department of Medicine, McGill University, 3755 Cote St. Catherine Road, Montreal, Quebec H3T 1E2, Canada.

Insulin-like growth factor I (IGF-I) is a mitogen for human breast cancer cells both in vivo and in vitro. We demonstrate here that the antiestrogen ICI 182780 (ICI) at 10(-8) m decreases IGF-I receptor (IGF-IR) mRNA levels by 70% after treatment for 48 h. Measurements of mRNA stability indicate that the half-life of IGF-IR mRNA is approximately 3 h. Estradiol treatment increases the half-life of the IGF-IR mRNA to approximately 6 h and the level of IGF-IR gene transcription by 1.8-fold, whereas ICI treatment not only decreases the IGF-IR transcription rate by 50% but also decreases the IGF-IR mRNA half-life to less than 3 h. Affinity labeling studies with [125I]-IGF-I show 35% increased labeled IGF-I to MCF-7 cell membrane following estradiol treatment and 40% decreased labeling following ICI treatment. We also demonstrate that ICI attenuates IGF-I-stimulated growth. Our data suggest that attenuation of IGF-I responsivity by ICI may be due in part to reducing the IGF-IR expression.

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