REGULATION OF INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS IN OVARIAN-CANCER CELLS BY ESTROGEN

Insulin-like growth factor-I (IGF-I), its receptor and its binding pro teins are expressed by ovarian cancer cells. In this study, we examine d oestradiol (E(2)) regulation of IGF-I and IGF binding proteins (IGFB P) in an oestrogen-responsive ovarian cancer cell line, PE04. In serum -free conditions, PE04 cell monolayer growth was increased 1.64-fold b y 3 nmol/l E(2) compared with controls, although IGF-I mRNA levels wer e not increased. In contrast to IGF-I mRNA, IGFBP mRNA was regulated b y E(2). E(2) caused a marked decrease in IGFBP-3 RNA, but IGFBP-2, -4 and -6 levels were only minimally depressed. IGFBP-5 mRNA levels were increased by E(2). Tamoxifen had less effect on IGFBP mRNA regulation. Ligand blotting showed that E(2) reduced IGFBP levels in conditioned media. IGFBP RNA was also detected in human ovarian tissue samples. Th us, IGFBP expression can be regulated in oestrogen-responsive ovarian cancer by E(2).