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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Inducible silencing of KILLER/ DR5 in vivo promotes bioluminescent colon tumor xenograft growth and confers resistance to chemotherapeutic agent 5-fluorouracil.

The candidate tumor suppressor KILLER/ DR5 is a DNA damage-inducible p53-regulated death receptor for the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a promising agent for cancer therapy. The majority of studies on KILLER/ DR5 have been focused on its role in TRAIL-induced apoptosis. However, its contribution to the inhibition of tumor growth and its role as a determinant of chemosensitivity are poorly understood. In the present study, we have generated stable human colon cancer cell lines, in which the function of KILLER/ DR5 was ablated using inducible RNA interference. Inducible silencing of KILLER/ DR5 in vivo by exposure of mice to doxycycline led to accelerated growth of bioluminescent tumor xenografts and conferred resistance to the chemotherapeutic agent 5-fluorouracil. Our results suggest that KILLER/ DR5 may be a critical determinant for tumorigenicity and chemosensitivity.[1]


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