Tamoxifen interaction with estrogen receptors

The anti-estrogen, tamoxifen, is the most commonly used hormonal therapy for breast cancer and has demonstrated positive effects on the cardiovascular and skeletal systems of postmenopausal women but is associated with an increased risk of uterine cancer. Tamoxifen is described as a SERM, a selective estrogen receptor modulator with a tissue selective profile that is caused by the different distribution of the a- and /3-subtypes of the estrogen receptor (ERa and ER/3) that activate and inhibit transcription respectively (77). These selective effects have been ascribed to differential interactions with gene promotor elements and coregulatory proteins depending on whether the ERa interacts directly, or in a tethered manner with DNA (78). In uterine tissue, tamoxifen interacts with a specific coactivator, SRCl, that is abundant in uterine tissue. 

Shiau AK, Barstad D, Loria PM, Cheng L, Kushner PJ, Agard A, Greene GL (1998) The structural basis of estrogen receptor/co-activator recognition and the antagonism of this interaction with tamoxifen. Cell 5 927-937... 

Yamamoto, Y., Wada, O., Suzawa, M., Yogiashi, Y., Yano, T., Kato, S. and Yanagisawa, J. (2001) The tamoxifen-responsive estrogen receptor a mutant D351Y shows reduced tamoxifen-dependent interaction with corepressor complexes. The Journal of Biological Chemistry, 276, 42684—42691. 

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