SXR: A Target for Breast Cancer Prevention and Treatment
Annual rept. 11 Mar 2002-10 Mar 2003
CALIFORNIA UNIV IRVINE
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Anti-estrogens such as tamoxifen are important therapeutic agents in the treatment and chemoprevention of breast cancers. Other compounds such as phytoestrogens, fatty acid amides such as anandamide and retinoid X receptor RXR agonists are also effective against breast cancer in cell lines and in animal models. Because these compounds are unrelated, it has not been appreciated that they might act through a common mechanism. These compounds all share the ability to activate a heterodimer of the steroid and xenobiotic receptor SXR and RXR. Our hypothesis is that SXR serves as a common molecular target for some of the anti-proliferative effects of these compounds and that activation of SXR is itself anti-proliferative. To this end, we have found that a constitutively active form of SXR, vpl6-SXR is able to slow the growth of transiently transfected breast cancer cells similar to treatment with SXR activators, and we are in the process of constructing stable cell lines with controlled expression of VPl6-SxR to confirm this result. We have detected the expression of SXR in ductal carcinomas, but not in normal breast tissue raising the possibility that the presence or absence of SXR may be related to breast cancer treatment outcome.
- Medicine and Medical Research