Chunk #65 — 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 vitro studies from Chock et al. showed that Wip1 can cooperate with BRCA1-IRIS to transform human mammary epithelial (HME) cells. As described in section 3.2.2, BRCA1-IRIS enhances Wip1 expression through HuR-dependent stabilization of Wip1 mRNA. The authors also showed that expression of BRCA1-IRIS and Wip1 significantly increased cellular transformation of HME cells, as measured by the number of cells and colonies in soft agar assay after co-overexpresson of BRCA1-IRIS and Wip1 (43). In addition, co-overexpression of Ras and Wip1, which previously had been shown to cooperate in tumorigensis (17, 18), increased cell and colony numbers in the soft agar assay to the same extent as BRCA1-IRIS/Wip1 co-overexpression (43). Since overexpression of Wip1 in the mammary tissue of mice did not induce mammary tumorigenesis (37), this study indicates that Wip1, through an unknown mechanism, cooperates with BRCA1-IRIS to promote tumorigenesis.
