Estrogen and progesterone regulate secretion of insulin-like growth factor binding proteins by human breast cancer cells.

We examined the effects of estradiol and progesterone agonist, promegestone (R5020), on secretion of insulin-like growth factors (IGF) and binding proteins (IGFBPs) by T-47D human breast cancer cells cultured in a serum-free defined medium. Estrogen, IGF-I and IGF-II promoted and R5020 inhibited growth under these conditions. Cells secreted IGFs and four IGFBPs. The amounts of all IGFBPs in cell-conditioned media were increased by estradiol and reduced by R5020, which also abolished the stimulatory effect of estradiol on IGFBPs without inducing an IGFBP protease. Therefore estrogen and progesterone may alter growth of breast cancers by regulating tumour secretion of IGFBPs and hence change carcinoma responsiveness to IGFs.