We created fusion chimeras between GR and other nuclear receptors that manifest ligand dependent cytoplasmic/nuclear translocation for the chimeric receptor in response to the heterologous ligand. The approach has been successfuly developed for the retinoic acid receptor (RAR), the estrogen receptor (ER), and the progesterone receptor (PR), and the thyroid hormone receptor (ThR). We developed cell lines which express fluorescently tagged versions of the receptor chimeras, and shown that U.S. water supplies are heavily contaminated with chemicals that have glucocorticoid and androgen activity. We believe that this approach can be generalized to many members of the nuclear receptor super-family, opening a new avenue for characterizatuib of water supply contaminaton.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010308-15
Application #
8763070
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
15
Fiscal Year
2013
Total Cost
$341,548
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Stavreva, Diana A; Wiench, Malgorzata; John, Sam et al. (2009) Ultradian hormone stimulation induces glucocorticoid receptor-mediated pulses of gene transcription. Nat Cell Biol 11:1093-102
Voss, Ty C; Hager, Gordon L (2008) Visualizing chromatin dynamics in intact cells. Biochim Biophys Acta 1783:2044-51
Sung, Myong-Hee; Bagain, Lorena; Chen, Zhong et al. (2008) Dynamic effect of bortezomib on nuclear factor-kappaB activity and gene expression in tumor cells. Mol Pharmacol 74:1215-22