Effects of inducible overexpression of DNp73(alpha) on cancer cell growth and response to treatment in vitro and in vivo

The p73 gene has a complex regulation, which leads to the expression of different isoforms, often with opposite biological effects. We have generated in the human colocarcinoma cell line HCT116, expressing a wild-type p53, an inducible DNp73(alpha) expressing system. Two clones (HCT116/DN3 and HCT116/DN14), upon doxycycline addition, show a strong expression of DNp73(alpha). In vitro the two DNp73(alpha) overexpressing clones grow at similar rate of the control transfected clone (HCT116/8a) and similarly respond to DNA damage. When injected in mice, HCT116/DN3, HCT116/DN14, and HCT116/8a cells grew similarly in the absence or presence of tetracycline. In HCT116/DN3 and HCT116/DN14 tumors, tetracycline induced a strong expression of DNp73(alpha) both as mRNA and protein. These results indicate that in this system the overexpression of the DNp73(alpha) does not induce a more aggressive phenotype and does not seem to be associated with a reduced response of the cells to treatment with anticancer agents. (copyright) 2005 Nature Publishing Group. All rights reserved.