Chunk #63 — 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
In addition to breast cancer, studies of additional types of cancers, such as neuroendocrine tumors (NETs) and medulloblastomas, indicate that inhibition of p53 may be an important function for Wip1 in tumorigenesis. NETs rarely have mutated p53, but Hu et al. showed that the majority of pancreatic neuroendocrine tumors express higher levels of p53-negative regulators such as Wip1 (108). In this study, the authors showed that 51% of pancreatic NETs have amplified PPM1D, which correlates with a high level of Wip1 mRNA expression (108). Wip1 is also overexpressed in medulloblastomas (103, 104), and Castellino et al. showed that Wip1 is amplified in 7 out of 11 primary medulloblastoma tumors analyzed, which correlated with high Wip1 expression. Furthermore, Wip1 inhibits basal and etoposide-induced p53-mediated apoptosis in medulloblastoma cells (105), implicating Wip1 as a positive regulator of medulloblastoma cell survival.
