Signaling by estrogens and tamoxifen in the human endometrium

Tamoxifen is used as adjuvant treatment for postmenopausal breast cancer patients. The mechanism of action of tamoxifen in breast cancer patients is that tamoxifen inhibits growth of cancer cells by competitive antagonism for estrogens at the estrogen receptor (ER). In the endometrium, tamoxifen has...

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Bibliographic Details
Published in:Journal of steroid biochemistry and molecular biology 2008-04, Vol.109 (3), p.219-223
Main Authors: Gielen, Susanne C.J.P., Santegoets, Lindy A.M., Hanifi-Moghaddam, Payman, Burger, Curt W., Blok, Leen J.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Carcinogenesis, carcinogens and anticarcinogens
Chemical agents
Cluster Analysis
Endometrium
Endometrium - drug effects
Endometrium - metabolism
Estrogen
Estrogens - metabolism
Female
Gene expression
Gene Expression Profiling
Gene Expression Regulation
Humans
Medical sciences
Polyps - pathology
Signal Transduction - drug effects
Tamoxifen
Tamoxifen - pharmacology
Tumors
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Summary:Tamoxifen is used as adjuvant treatment for postmenopausal breast cancer patients. The mechanism of action of tamoxifen in breast cancer patients is that tamoxifen inhibits growth of cancer cells by competitive antagonism for estrogens at the estrogen receptor (ER). In the endometrium, tamoxifen has an effect that varies with the ambient concentration of estrogen: in premenopausal women (high estrogen levels), tamoxifen displays an estrogen-antagonistic effect, while in postmenopausal women (low estrogen levels), tamoxifen displays an estrogen-agonistic mode of action. Here, using microarray technology we have compared estrogen signaling with tamoxifen signaling in the human endometrium. It was observed that on the one hand tamoxifen-treatment results in modulation of expression of specific genes (370 genes) and on the other hand tamoxifen-treatment results in modulation of a set of genes which are also regulated by estrogen treatment (142 genes). Upon focusing on regulation of proliferation, we found that tamoxifen-induced endometrial proliferation is largely accomplished by using the same set of genes as are regulated by estradiol. So, as far as regulation of proliferation goes, tamoxifen seems to act as estrogen agonist. Furthermore, tamoxifen-specific gene regulation may explain why tamoxifen-induced endometrial tumors behave more aggressively than sporadic endometrial tumors.
ISSN:0960-0760
1879-1220
DOI:10.1016/j.jsbmb.2008.03.021