Regression of DMBA-induced breast carcinoma following ovariectomy is associated with increased expression of genes encoding insulin-like growth factor binding proteins.
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.
Nickerson
T
T
Cancer Prevention Unit of the Jewish General Hospital and Departments of Oncology and Medicine, McGill University, Montreal, Quebec H3T 1E2, Canada.
Zhang
J
J
Pollak
M
M
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D015152:Blotting, Northern; D005260:Female; D015870:Gene Expression; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced / Q000235:genetics / Q000601:surgery*; D010052:Ovariectomy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D015127:9,10-Dimethyl-1,2-benzanthracene; D007334:Insulin-Like Growth Factor I