Activity of any class IA PI3K isoform can sustain cell proliferation and survival.

ABSTRACT: Small molecule inhibitors of PI3K for oncology mainly target the class I PI3Ks, comprising the p110alpha, beta, gamma, and delta isoforms, of which only p110alpha is mutated in cancer. To assess the roles of class I PI3K isoforms in cell proliferation and survival, we generated immortalized mouse leukocyte and fibroblast models in which class I PI3Ks were inactivated by genetic and pharmacological approaches. In IL3-dependent hemopoietic progenitor cells (which express all four class I PI3K isoforms), genetic inactivation of either p110alpha or p110delta did not affect cell proliferation or survival or sensitize to p110beta or p110gamma inactivation. Upon compound inactivation of p110alpha and p110delta, which removed >90% of p85-associated PI3K activity, remarkably, cells continued to pro

SUBMITTER: Foukas LC 

PROVIDER: S-EPMC2895061 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature