title: Nongenomic effect of estrogen on the MAPK signaling pathway and calcium influx in endometrial carcinoma cells.
abstract: 17beta-Estradiol (E2) is well known to interact with intracellular receptors that act as nuclear transcription factors. However, abundant evidence now indicates that E2 can also rapidly induce several nongenomic effects through signaling pathways related to cell growth, preservation, and differentiation. We studied the nongenomic effects of E2 in two human endometrial carcinoma cell lines, Ishikawa (estrogen receptor (ER) positive) and Hec-1A (ER negative or low) by cultivating them with either E2 or its membrane-impermeable conjugate, E2-BSA. We found that phosphorylation of Erk1/2 could be induced by either E2 or E2-BSA in Ishikawa cells. In Hec-1A cells, only E2 was able to induce Erk1/2 phosphorylation. Although the existence of a nongenomic component to the response was indicated by the finding that it could not be completely inhibited by the ER antagonist ICI182780,and it can also be inhibited by calcium inhibitor Nifedipine partly. Phosphorylation of Akt could not be induced, either by E2 or E2-BSA, in either cell line. Both E2 and E2-BSA elicited calcium influx in Ishikawa cells. In contrast to these nongenomic effects, only E2 was able to stimulate expression of the anti-apoptotic-protein Bcl-2. Taken together, these data indicate that nongenomic effects such as Erk1/2 phosphorylation and calcium influx can be initiated from the membrane in Ishikawa cell, and calcium can activate Erk1/2 phosphorylation. Except for ER, there must be other binding location of estrogen in endometrial cancer cells, and the nongenomic effects of estrogen initiated from plasma membrane by E2-BSA cannot lead to transcriptional effect of Bcl-2 expression.
authors.affiliation: Department of Gynecology, Peking University People's Hospital, Xi Cheng District, Beijing, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Li
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhao
authors.forename: Lifang
authors.initials: L
authors.lastname: Zhang
authors.forename: Guo
authors.initials: G
authors.lastname: Zhang
authors.forename: Jianliu
authors.initials: J
authors.lastname: Wang
authors.forename: Lihui
authors.initials: L
authors.lastname: Wei
mesh_terms: D001665:Binding Sites; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D004967:Estrogens; D019253:Proto-Oncogene Proteins c-bcl-2; D004958:Estradiol; D048052:Mitogen-Activated Protein Kinase 3; D002118:Calcium