@entity19 expressing the polyomavirus (PyV) @entity2172 ( @entity2172 ) develop multifocal @entity5 which frequently metastasize to the lung. The potent transforming activity of PyV @entity2172 is correlated with its capacity to activate and associate with a number of signaling molecules, including the Src family @entity669 kinases, the 85-kDa Src homology 2 subunit of the @entity4357 3' (PI-3') kinase, and the @entity54310 adapter protein. To uncover the role of these signaling proteins in @entity2172 -mediated mammary tumorigenesis, we have generated @entity19 that express mutant PyV @entity2172 antigens decoupled from either the @entity54310 or the PI-3' kinase signaling pathway. In contrast to the rapid induction of metastatic @entity5 observed in the strains expressing wild-type PyV @entity2172 , mammary epithelial cell-specific expression of either mutant PyV @entity2172 resulted in the induction of extensive @entity2543 . The @entity2543 expressing the mutant PyV @entity2172 defective in recruiting the PI-3' kinase were highly apoptotic, suggesting that recruitment of PI-3' kinase by @entity2172 affects cell survival. Whereas the initial phenotypes observed in both strains were global @entity2543 , focal @entity5 eventually arose in all female @entity19 . Genetic and biochemical analyses of tumorigenesis in the transgenic strains expressing the PyV @entity2172 mutant lacking the @entity54310 binding site revealed that a proportion of the @entity3 arising in these @entity19 displayed evidence of reversion of the mutant @entity54310 binding site. In contrast, no evidence of reversion of the PI-3' kinase binding site was noted in @entity5 derived from the strains expressing the PI-3' kinase binding site @entity2172 mutant. @entity5 progression in both mutant strains was further correlated with upregulation of the epidermal growth factor receptor family members which are known to couple to the PI-3' kinase and @entity54310 signaling pathways. Taken together, these observations suggest that PyV @entity2172 -mediated tumorigenesis requires activation of both @entity54310 and PI-3' kinase, which appear to be required for stimulation of cell proliferation and survival signaling pathways, respectively.

Requirement for both @entity54310 and XXXX 3' kinase signaling pathways in polyomavirus middle T-mediated mammary tumorigenesis.

@entity2172 :: ('MESH:D010033', 'Disease') :: ['middle T antigen', 'MT'] @entity19 :: ('10090', 'Species') :: ['mice', 'Transgenic mice', 'transgenic mice'] @entity5 :: ('MESH:D009369', 'Disease') :: ['mammary tumors', 'Tumor', 'tumors'] @entity54310 :: ('20416(Tax:10090)', 'Gene') :: ['Shc'] @entity2543 :: ('MESH:D017573', 'Disease') :: ['mammary epithelial hyperplasias'] @entity3 :: ('MESH:D009362', 'Disease') :: ['metastatic tumors'] @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine'] @entity4357 :: ('MESH:D010716', 'Chemical') :: ['phosphatidylinositol']
@entity4357 :: (MESH:D010716,Chemical) :: ['phosphatidylinositol']
