Abstract 3180: Regulation of stem cells by the tumor suppressor PP2A-B56{alpha}

Protein phosphatase 2 A (PP2A) is one of the major cellular Serine-Threonine phosphatases and regulates numerous signaling pathways, including stem cell self-renewal, proliferation, differentiation, and cell survival. The PP2A holoenzyme has 3 subunits: a catalytic (C) subunit, a structural (A) subunit, and a variable regulatory (B) subunit, which directs PP2A to specific targets. PP2A inhibition is required to completely transform human cells and siRNA screens have shown that loss of B56α, B56γ, or PR72/PR130 B subunits results in cell transformation, which are involved in negatively regulating oncogenic pathways including Wnt, Akt, and Myc. Moreover, PP2A plays an important role in regulating human embryonic stem cells, where both the A and C subunit levels and PP2A activity gradually increase during the course of differentiation. Our preliminary data also demonstrates in breast cancer cell lines that B56α overexpression decreases the number of mammospheres whereas inhibiting B56α increases them. Further research is needed to address the function of specific PP2A complexes in regulating stem cells. Despite the fact that B56α depletion is important for human cell transformation, no one has reported on its role in vivo and no mouse model has ever been generated to our knowledge. Therefore, to study the role of B56α in stem cells and cell transformation in vivo, we have generated B56α knockout mice.We generated B56α knockout mice using commercially available gene trap ...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Immunology Source Type: research