Browsing by Subject "Epithelial cells"
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Item Mouse mammary tumor virus activates Cdc42 leading to filopodia formation and transformation of mammary epithelial cells(2005) Smith, Gail Perry; Poenie, Martin F.Mouse mammary tumor virus (MMTV) is a B type retrovirus characterized by assembly of viral “A” particles in the cytoplasm that move to the membrane where they acquire an envelope and exit the cell. Viral exit is associated with reorganization of cortical actin and accumulation of virus in filamentous projections at the cell surface. Here we show that MMTV egress and exit from the cell depends on actin polymerization mediated by the activation of Cdc42 and WASP. Cytochalasin B treatment blocked both accumulation of virus in filopodia and viral exit. Active virus production correlated with accumulation of activated Cdc42 and MMTV Gag on immobilized Pak columns. Both Cdc42 and WASP co-localized with virus particles in the cytoplasm and at the cell surface. Alternatively, dominant-negative Cdc42 or a mutant WASP construct without the Cdc42-binding domain failed to co-localize with virus and prevented MMTV-induced cytoskeletal reorganization as well as viral egress and exit. Infection with virus conferred on these cells the ability to grow in serum-free media, to grow on soft agar and to form foci, features indicative of transformation. Uninfected cells expressing constitutively active Cdc42 exhibited similar characteristics. Furthermore, dominant negative Cdc42 blocked transformation by MMTV. These findings suggest that activation of the Cdc42/WASP/ARP2/3 pathway is required for viral exit and that viral activation of Cdc42 is both required and sufficient to cause transformation.