Genomic and nongenomic effects of estrogen signaling in human endometrial cells: involvement of the growth factor receptor signaling downstream AKT pathway.
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.
Gielen
Sussane C J P
SC
Department of Obstetrics and Gynecology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Santegoets
Lindy A M
LA
Kühne
Liesbeth C M
LC
Van Ijcken
Wilfred F J
WF
Boers-Sijmons
Bianca
B
Hanifi-Moghaddam
Payman
P
Helmerhorst
Theo J M
TJ
Blok
Leen J
LJ
Burger
Curt W
CW
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*
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