INVIVO INHIBITION OF INSULIN-LIKE GROWTH FACTOR-I GENE-EXPRESSION BY TAMOXIFEN

Tamoxifen, a partial antagonist to the estrogen receptor, is widely us ed 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 administratio n is associated with a reduction of serum insulin-like growth factor I (IGF-I) concentration. We demonstrate here that tamoxifen, when admin istered in an in vivo experimental system previously used to demonstra te its cytostatic effect on breast cancer cell proliferation, inhibits the expression of the IGF-I gene in common target organs for breast c ancer metastasis. Furthermore, while our prior experimental studies ha ve demonstrated an inhibitory effect of tamoxifen on growth hormone ou tput, we show here for the first time that the suppression of IGF-I ge ne expression associated with tamoxifen administration is in part a co nsequence of a pituitary-independent action of the drug. Because IGF-I is a potent mitogen for breast cancer cells, this newly described act ivity of tamoxifen may contribute to its antineoplastic properties, pa rticularly with regard to inhibition of metastasis seen both in animal models and clinically.