RESUMEN
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.
Asunto(s)
Proteínas Portadoras/metabolismo , Estradiol/farmacología , Factor II del Crecimiento Similar a la Insulina/metabolismo , Promegestona/farmacología , Somatomedinas/metabolismo , Neoplasias de la Mama , Proteínas Portadoras/análisis , División Celular/efectos de los fármacos , Medio de Cultivo Libre de Suero , Femenino , Humanos , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina , Factor II del Crecimiento Similar a la Insulina/análisis , Factor II del Crecimiento Similar a la Insulina/farmacología , Radioinmunoensayo , Células Tumorales CultivadasRESUMEN
Insulin-like growth factors (IGF) and binding proteins were measured in serum from pregnant and nonpregnant women. IGF-I determined by immunoassay after acid-ethanol extraction was increased by pregnancy (p less than 0.005) and was highest in the third trimester (p less than 0.01). Size exclusion chromatography of serum in acid before assay (i) gave a very similar IGF-I pattern, (ii) showed that IGF-II was much higher than IGF-I and (iii) revealed less serum IGF-binding protein activity in pregnancy and lactation. All IGF-binding proteins except binding protein-1 were markedly reduced by pregnancy. This indicates a major change in the main carrier protein for IGFs in the circulation and suggests that tissue targetting of IGFs may be altered during pregnancy.