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In Vivo Inhibition of Insulin-like Growth Factor I Gene Expression by Tamoxifen¹

Departments of Medicine and Oncology, McGill University [M. P.], and the Lady Davis Institute for Medical Research of the Sir Mortimer B. Davis-Jewish General Hospital [M. P., H. T. H., E. T., L. W.], Montréal. Québec, Canada

Tamoxifen, a partial antagonist to the estrogen receptor, is widely used in the treatment of breast cancer and is currently being evaluated as a breast cancer preventative agent in large-scale clinical trials. Recent clinical research has demonstrated that tamoxifen administration is associated with a reduction of serum insulin-like growth factor I (IGF-I) concentration. We demonstrate here that tamoxifen, when administered in an in vivo experimental system previously used to demonstrate its cytostatic effect on breast cancer cell proliferation, inhibits the expression of the IGF-I gene in common target organs for breast cancer metastasis. Furthermore, while our prior experimental studies have demonstrated an inhibitory effect of tamoxifen on growth hormone output, we show here for the first time that the suppression of IGF-I gene expression associated with tamoxifen administration is in part a consequence of a pituitary-independent action of the drug. Because IGF-I is a potent mitogen for breast cancer cells, this newly described activity of tamoxifen may contribute to its antineoplastic properties, particularly with regard to inhibition of metastasis seen both in animal models and clinically.

¹ Supported by grants to M. P. by the National Cancer Institute of Canada and the Canadian Breast Cancer Foundation.

² To whom requests for reprints should be addressed, at Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, 3755 Côte Ste-Catherine Road, Montréal, Québec, Canada H3T 1E2.

Received 12/23/92. Accepted 3/ 5/93.

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