The Role of Ca2+ and Calmodulin in Estrogen Receptor Function and Tamoxifen Resistance
Annual rept. 1 Apr 2002-31 Mar 2003
BRIGHAM AND WOMEN'S HOSPITAL BOSTON MA
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The purpose of this proposal is to evaluate the participation of Ca2 and calmodulin in estrogen receptor ER function and tamoxifen resistance. The focus is directed towards the interaction between calmodulin and ER in ER signaling, as well as the possible involvement of Ca2 and calmodulin in tamoxifen resistance. Major findings to date are i calmodulin binds directly to ER and stabilizes the receptor ii calmodulin protects ER from degradation in the proteasome pathway iii calmodulin is necessary for estrogen-stimulated transcriptional activation by ER iv the effect of calmodulin in ER transcriptional activation is independent of its effect on ER stability and v inhibition of calmodulin function in the nucleus, but not at the plasma membrane, eliminates estrogen-induced transcriptional activation by ER. These data reveal that calmodulin is a component of both ER stability and ER transcriptional activity. This information could have potential therapeutic implications in patients with breast cancer.
- Medicine and Medical Research