Requirement for interaction of PI3-kinase p110α with RAS in lung tumor maintenance
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Esther Castellano Clare Sheridan May Zaw Thin Emma Nye Bradley Spencer-Dene Markus E Diefenbacher Christopher Moore Madhu S Kumar Miguel M Murillo Eva Gronroos François Lassailly Gordon Stamp Julian DownwardAbstract
RAS proteins directly activate PI3-kinases. Mice bearing a germline mutation in the RAS binding domain of the p110α subunit of PI3-kinse are resistant to the development of RAS-driven tumors. However, it is unknown whether interaction of RAS with PI3-kinase is required in established tumors. The need for RAS interaction with p110α in the maintenance of mutant Kras-driven lung tumors was explored using an inducible mouse model. In established tumors, removal of the ability of p110α to interact with RAS causes long-term tumor stasis and partial regression. This is a tumor cell-autonomous effect, which is improved significantly by combination with MEK inhibition. Total removal of p110α expression or activity has comparable effects, albeit with greater toxicities.
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Publisher website (DOI) 10.1016/j.ccr.2013.09.012
Europe PubMed Central 24229709
Pubmed 24229709
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