Investigating the duality of Inpp4b function in the cellular transformation of mouse fibroblasts

摘要

is a tumour suppressor in breast, ovarian, prostate, thyroid and other cancers, attributed to its ability to reduce oncogenic Akt-signaling. However, emerging studies show that also has tumour-promoting properties in cancers including acute myeloid leukemia, colon cancer, melanoma and breast cancer. Together these findings suggest that may be a context dependent cancer gene. Whether functions solely in a tumour suppressing or tumour promoting manner, or both in non-transformed cells is currently not clear. In this study, consequences of deficiency and overexpression of on cellular transformation was investigated using a mouse embryonic fibroblast (MEF) model of cellular transformation. We observed that neither deficiency nor overexpression of was sufficient to induce neoplastic transformation, alone or in combination with or overexpression. However, -deficiency did cooperate with -mediated cellular transformation, a finding which was associated with increased phosphorylated-Akt levels. Transformation and phosphorylated-Akt levels were dampened upon overexpression of in -MEF. Together, our findings support a model where INPP4B function suppresses transformation mediated by , but is inconsequential for and mediated transformation.