Chunk #60 — 4. WIP1 SUPPRESSES THE STRESS RESPONSE: UPDATE — 4.5. Wip1 attenuates the response to oncogenic stress and promotes tumorigenesis — 4.5.1. Cooperation of Wip1 with oncogenes in tumorigenesis
Many human cancers exhibit amplification of the PPM1D gene or overexpression of the Wip1 protein. As shown in Table 2, these include breast cancer, ovarian clear cell adenocarcinoma, neuroblastoma, medulloblastoma, gastric carcinoma and pancreatic adenocarcinoma (11, 13, 14, 17, 98–106). Further work using mouse models validated Wip1 as an oncogene, and this has been reviewed by Lu et al. (25). For example, Bulavin et al. showed that deletion of PPM1D inhibited Erbb2 and Hras1 tumor formation through a p38 MAPK and p16/p19 mechanism (18). However, Wip1 is a proto-oncogene, since overexpression of Wip1 along with other oncogenes enhances in vitro oncogenic transformation and tumorigenesis whereas Wip1 overexpression alone has no effect (17, 37). In addition, several recent studies described below have investigated Wip1 as an oncogene.
