Effects of tamoxifen and ethynylestradiol cotreatment on uterine gene expression in immature, ovariectomized mice.

Journal of Molecular Endocrinology
Cora J FongTimothy R Zacharewski

Abstract

Tamoxifen (TAM), the primary treatment for estrogen receptor (ER)-positive breast cancer, has been associated with an increased incidence of endometrial cancer in postmenopausal, but not premenopausal women. TAM elicits a partial ER-mediated uterotrophic response in immature rodents when compared with ethynylestradiol (EE), a potent ER agonist. However, cotreatment with 1000 microg/kg TAM antagonizes the uterotrophic effect induced by 30 microg/kg EE. To further investigate the anti-uterotrophic activity of TAM, immature, ovariectomized C57BL/6 mice were treated with a single oral dose of EE, TAM, EE+TAM, or vehicle, and harvested at 2, 4, 8, 12, 18, and 24 h or after three daily treatments at 72 h. Significant increases in uterine wet weight (UWW) were observed at 18 h for EE, TAM, and the mixture. However, mixture induction of UWW was significantly lower when compared with EE-induced uterotrophy at 72 h. This inhibitory effect is also reflected in decreases in luminal circumference, yet EE-induced luminal epithelial cell height was unaffected by cotreatment with TAM. Gene expression analysis using a 2 x 2 factorial cDNA microarray study design identified 2518 differentially expressed genes following EE treatment alone. Howeve...Continue Reading

Citations

Jul 31, 2013·Journal of Molecular Endocrinology·Margarita M IvanovaCarolyn M Klinge
Oct 8, 2013·Toxicology and Applied Pharmacology·Joshua C KwekelTimothy R Zacharewski
Jun 12, 2012·Experimental Gerontology·M DreyUNKNOWN FiAT intervention group
Nov 26, 2014·Menopause : the Journal of the North American Menopause Society·David F ArcherGinger D Constantine
Apr 13, 2017·Journal of Bioenergetics and Biomembranes·Carolyn M Klinge

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