Regression of DMBA-induced breast carcinoma following ovariectomy is associated with increased expression of genes encoding insulin-like growth factor binding proteins.
- T Nickerson
- J Zhang
- M Pollak
Affiliations: Cancer Prevention Unit of the Jewish General Hospital and Departments of Oncology and Medicine, McGill University, Montreal, Quebec H3T 1E2, Canada.
- Published online on: May 1, 1999 https://doi.org/10.3892/ijo.14.5.987
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Insulin-like growth factor I (IGF-I) has well characterized mitogenic and antiapoptotic effects in both normal and neoplastic mammary epithelial cells which are mediated through the IGF-I receptor. IGF activity is modulated by a family of high affinity IGF binding proteins (IGFBPs 1-6). Here we show that gene expression of IGFBP-2, -3, -4 and -5 increases rapidly in DMBA-induced rat mammary tumors following ovariectomy. We observed a 90% reduction in volume of DMBA-induced rat mammary tumors by 14 days post-ovariectomy. The time course of maximal tumor regression was associated with increased gene expression of IGFBPs, as detected by Northern blot analysis. IGFBP-2, -3, -4 and -5 mRNA levels increased from 2- to 16-fold of control by 14 days of estrogen-ablation. These results are compatible with the hypothesis that response of DMBA-induced mammary tumors to estrogen deprivation therapies involves reduction of IGF bioactivity secondary to upregulation of expression of IGF binding proteins.