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  • Requirement for interaction of PI3-kinase p110α with RAS in lung tumor maintenance.

Requirement for interaction of PI3-kinase p110α with RAS in lung tumor maintenance.

Cancer cell (2013-11-16)
Esther Castellano, Clare Sheridan, May Zaw Thin, Emma Nye, Bradley Spencer-Dene, Markus E Diefenbacher, Christopher Moore, Madhu S Kumar, Miguel M Murillo, Eva Grönroos, Francois Lassailly, Gordon Stamp, Julian Downward
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Tamoxifen citrate for performance test, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Tamoxifen citrate salt, ≥99%
Tamoxifen citrate, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Tamoxifen, ≥99%