PMID- 17045571 OWN - NLM STAT- MEDLINE DCOM- 20061218 LR - 20131121 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 350 IP - 4 DP - 2006 Dec 1 TI - Estradiol regulates the insulin-like growth factor-I (IGF-I) signalling pathway: a crucial role of phosphatidylinositol 3-kinase (PI 3-kinase) in estrogens requirement for growth of MCF-7 human breast carcinoma cells. PG - 916-21 AB - Estrogens can stimulate the proliferation of estrogen-responsive breast cancer cells by increasing their proliferative response to insulin-like growth factors. With a view to investigating the molecular mechanisms implicated, we studied the effect of estradiol on the expression of proteins implicated in the insulin-like growth factor signalling pathway. Estradiol dose- and time-dependently increased the expression of insulin receptor substrate-1 and the p85/p110 subunits of phosphatidylinositol 3-kinase but did not change those of ERK2 and Akt/PKB. ICI 182,780 did not inhibit estradiol-induced IRS-1 and p85 expression. Moreover, two distinct estradiol-BSA conjugate compounds were as effective as estradiol in inducing IRS-1 and p85/p110 expression indicating the possible implication of an estradiol membrane receptor. Comparative analysis of steroids-depleted and steroids-treated cells showed that IGF-I only stimulates cell growth in the latter condition. Nevertheless, expression of a constitutively active form of PI 3-kinase in steroid-depleted cells triggers proliferation. These results demonstrate that estradiol positively regulates essential proteins of the IGF signalling pathway and put in evidence that phosphatidylinositol 3-kinase plays a central role in the synergistic pro-proliferative action of estradiol and IGF-I. FAU - Bernard, Laurence AU - Bernard L AD - Institut National de la Sante et de la Recherche Medicale, Unite 515, Croissance, Differenciation et Processus Tumoraux, Hopital Saint-Antoine, Paris, France. FAU - Legay, Christine AU - Legay C FAU - Adriaenssens, Eric AU - Adriaenssens E FAU - Mougel, Alexandra AU - Mougel A FAU - Ricort, Jean-Marc AU - Ricort JM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20061002 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Estrogens) RN - 4TI98Z838E (Estradiol) RN - 67763-96-6 (Insulin-Like Growth Factor I) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) SB - IM MH - Breast Neoplasms/*pathology/*physiopathology MH - Cell Proliferation MH - Dose-Response Relationship, Drug MH - Estradiol/*administration & dosage MH - Estrogens/*metabolism MH - Humans MH - Insulin-Like Growth Factor I/*metabolism MH - Phosphatidylinositol 3-Kinases/*metabolism MH - Signal Transduction/*drug effects EDAT- 2006/10/19 09:00 MHDA- 2006/12/19 09:00 CRDT- 2006/10/19 09:00 PHST- 2006/09/21 00:00 [received] PHST- 2006/09/22 00:00 [accepted] PHST- 2006/10/19 09:00 [pubmed] PHST- 2006/12/19 09:00 [medline] PHST- 2006/10/19 09:00 [entrez] AID - S0006-291X(06)02168-1 [pii] AID - 10.1016/j.bbrc.2006.09.116 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2006 Dec 1;350(4):916-21. doi: 10.1016/j.bbrc.2006.09.116. Epub 2006 Oct 2.