Regulation of vascular endothelial growth factor by tamoxifen in vitro and in vivo.
OBJECTIVE
To evaluate the effects of tamoxifen on human endometrial vascular endothelial growth factor (VEGF) gene expression in vitro and in vivo.


METHODS
Ishikawa cells were transiently co-transfected with plasmids expressing human estrogen receptor (ER)-alpha or -beta and a 2.3-kb human VEGF promoter-luciferase construct. Transfected cells were treated with tamoxifen and the increase in luciferase activity was compared to controls. In addition, immunohistochemical analysis of VEGF expression in endometrial biopsies from 11 postmenopausal women receiving tamoxifen was compared to 24 postmenopausal women on no hormone replacement.


RESULTS
In transfected cells expressing ERalpha, tamoxifen induced a significant VEGF promoter activation (3.2-fold, p < 0.01), whereas cells expressing ERbeta showed a 1.6-fold stimulation (p = NS). No significant differences in VEGF immunostaining were observed in tamoxifen-exposed women.


CONCLUSIONS
Although tamoxifen exposure increases VEGF expression in vitro, a significant increase in VEGF expression is not apparent in endometrial biopsies of postmenopausal women treated with this drug.
Mueller
Michael D
MD
Universitäts-Frauenklinik, Inselspital Bern, Switzerland. michel.mueller@insel.ch
Pritts
Elizabeth A
EA
Zaloudek
Charles J
CJ
Dreher
Ekkehard
E
Taylor
Robert N
RN
D001706:Biopsy; D004717:Endometrium / Q000737:chemistry; D016228:Endothelial Growth Factors / Q000032:analysis / Q000235:genetics*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics*; D008222:Lymphokines / Q000032:analysis / Q000235:genetics*; D017698:Postmenopause; D011401:Promoter Regions, Genetic; D011960:Receptors, Estrogen / Q000032:analysis / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins; D013629:Tamoxifen / Q000009:adverse effects / Q000494:pharmacology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D013629:Tamoxifen