Smaller Liver Tumors Without c-Jun

Abstract

The transcription factor c-Jun controls both cell proliferation and cell survival, and not surprisingly, its activity has been linked to various human tumors. However, although it appears to be proapoptotic in some tumor types, it displays antiapoptotic activity in others, as seen in liver cancer. Eferl et al. found that in a mouse model of liver carcinoma, deletion of c-Jun did not affect proliferation of liver tumor cells, but caused an increase in the number of apoptotic cells and a consequent decrease in liver tumor mass. By inducing deletion of c-Jun in mice at different times after liver tumor formation, the authors determined its requirement for tumor cell survival only in early stages of cancer development. Hepatocytes lacking c-Jun had increased expression of the tumor suppressor protein p53 and were also more sensitive to cell death induced by exposure to tumor necrosis factor (TNF). Hepatocytes lacking both c-Jun and p53 regained resistance to TNF-induced apoptosis, which suggests that c-Jun antagonizes the proapoptotic and antiproliferative activities of p53. Human liver tumors express high levels of c-Jun, and use of inhibitors in the early stages of this particular cancer may be therapeutically effective. R. Eferl, R. Ricci, L. Kenner, R. Zenz, J.-P. David, M. Rath, E. F. Wagner, Liver tumor development: c-Jun antagonizes the proapoptotic activity of p53. Cell 112 , 181-192 (2003). [Online Journal]