Nuclear Orphan Receptor TR3/Nur77 Mediates Melanoma Cell Apoptosis

Hong Yu, Suresh Kumar, Dong Fang, Geza Acs and XiaoWei Xu

volume 6 | issue 3

March 2007
Pages: 405 - 412

We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:

Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.

TR3 was originally recognized for its role in the regulation of cell survival and differentiation, however, it was recently found to be a potent pro-apoptotic protein. In order to characterize the role of TR3 in melanoma cell apoptosis, we studied expression of TR3 in melanoma cell lines and tissues, its subcellular distribution and function during apoptosis using various expression and RNA interference vectors. We found that TR3 was constitutively expressed in both cultured melanoma cells and melanoma tissues. TR3 expression was significantly decreased in advanced melanomas comparing to benign nevi. Over-expression of wild type TR3 or mutant TR3 lacking the DNA binding domain resulted in massive apoptosis in melanoma cells, whereas stable knockdown of TR3 using RNA interference resulted in melanoma cell resistance to apoptosis induced by chemotherapeutic agents ATRA and cisplatin. We further demonstrated that apoptosis in melanoma cells was mediated, at least partially, through TR3 mitochondrial translocation but not alteration in TR3 expression levels. Our results suggest that TR3 is an important apoptosis inducing factor in melanoma cells. Decreased expression of TR3 in metastatic melanoma cells may contribute to their reduced apoptotic potential and increased resistance to chemotherapy.

Authors

Hong Yu

University of Texas Southwestern Medical Center at Dallas, Dallas, Texas

Suresh Kumar

Univeristy of Pennsylvania; Philadelphia, Pennsylvania USA

Dong Fang

Wistar Institute; Philadelphia, Pennsylvania USA

Geza Acs

Moffitt Cancer Center; Tampa, Florida USA

XiaoWei Xu