Chaperone proteins have been identified that transport copper to various compartments in cells, but to date, none have been identified that traffic copper to the nucleus. Copper-64 (T1/2= 12.7 h) is a beta emitter, and copper radiopharmaceuticals have been identified for PET imaging and targeted radiotherapy of cancer. The delivery of 64Cu to the cell nucleus may enhance the therapeutic effect of tumor targeting copper radiopharmaceuticals. We previously demonstrated that HCT 116 p53+/+ cells accumulate more 64Cu in their nuclei than HCT 116 p53 -/- cells, suggesting a role for p53 in the transport of 64Cu to the nucleus.  Isolation of 64Cu-labeled proteins in HCT116 nuclei by chromatography followed by mass spectroscopy analysis identified Atox1 as a major 64Cu-binding protein, and MEF Atox1+/+ accumulate more 64Cu in the nucleus compared to Atox1-/- cells. Additionally, HCT116 cells pretreated with cisplatin overexpress Atox1 and increase the nuclear localization of 64Cu.

Roles of Atox1 and p53 in the delivery of copper-64 to tumor cell nuclei: Implications for cancer therapy

245th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.