Paper
Regulation of insulin-like growth factor binding proteins in ovarian cancer cells by oestrogen

https://doi.org/10.1016/0959-8049(93)90464-QGet rights and content

Abstract

Insulin-like growth factor-I (IGF-I), its receptor and its binding proteins are expressed by ovarian cancer cells. In this study, we examined oestradiol (E2) regulation of IGF-I and IGF binding proteins (IGFBP) in an oestrogen-responsive ovarian cancer cell line, PE04. In serum-free conditions, PE04 cell monolayer growth was increased 1.64-fold by 3 nmol/l E2 compared with controls, although IGF-I mRNA levels were not increased. In contrast to IGF-I mRNA, IGFBP mRNA was regulated by E2. E2 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 E2. Tamoxifen had less effect on IGFBP mRNA regulation. Ligand blotting showed that E2 reduced IGFBP levels in conditioned media. IGFBP RNA was also detected in human ovarian tissue samples. Thus, IGFBP expression can be regulated in oestrogen-responsive ovarian cancer by E2.

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      Furthermore, estradiol also increases the number of IGF-I receptors per cell by approximately 50% in cultures from HGSC mesenteric metastases [114]. A study that first reported IGFBP3 mRNA in human ovarian cancer samples shows that estradiol reduces levels of the IGF-I inhibitor, IGFBP3, in ERα-positive PEO4 cells [115]. In support of these studies, Walker et al. show that estradiol reduces IGFBP3 and IGFBP5 levels and increases IGFBP4 levels via ERα in PEO4 ovarian cancer cells, which is reversed by tamoxifen treatment.

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