title: Genomic and nongenomic effects of estrogen signaling in human endometrial cells: involvement of the growth factor receptor signaling downstream AKT pathway.
abstract: For the endometrium, estradiol and tamoxifen induce proliferation, and consequently, tamoxifen treatment of breast cancer results in a 2-fold to 7-fold increased risk for endometrial cancer. Here, the role of activation of growth factor receptor signaling in mediating the effects of estrogen and tamoxifen is determined. Microarray analysis of ECC-1 cells treated with estradiol or tamoxifen indicate that rapid responses to treatment (1 hour) are very distinct from long-term responses (>24 hours). Furthermore, estradiol and tamoxifen are observed to induce AKT activation. Comparing long-term estrogen- and tamoxifen-regulated genes with genes regulated by insulin-like growth factor 1 and amphiregulin reveals that the late effects of estrogen and tamoxifen signaling may partly be mediated via activation of growth factor receptor signaling pathways. It is hypothesized that both early and late effects of estrogen and tamoxifen signaling in the endometrium are partly mediated via the activation of growth factor receptor signaling, putatively at the level of AKT activation.
authors.affiliation: Department of Obstetrics and Gynecology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Sussane C J P
authors.initials: SC
authors.lastname: Gielen
authors.forename: Lindy A M
authors.initials: LA
authors.lastname: Santegoets
authors.forename: Liesbeth C M
authors.initials: LC
authors.lastname: Kühne
authors.forename: Wilfred F J
authors.initials: WF
authors.lastname: Van Ijcken
authors.forename: Bianca
authors.initials: B
authors.lastname: Boers-Sijmons
authors.forename: Payman
authors.initials: P
authors.lastname: Hanifi-Moghaddam
authors.forename: Theo J M
authors.initials: TJ
authors.lastname: Helmerhorst
authors.forename: Leen J
authors.initials: LJ
authors.lastname: Blok
authors.forename: Curt W
authors.initials: CW
authors.lastname: Burger
mesh_terms: D045744:Cell Line, Tumor; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: D004967:Estrogens; D017978:Receptors, Growth Factor; D013629:Tamoxifen; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt