Using GEM models, we tested whether PI3'-lipid signaling was limiting for the promotion of KRAS(G12D)-driven lung tumors by inducing the expression of KRAS(G12D) in the absence and presence of the activating PIK3CA(H1047R) mutation.
However, a more rigorous test of the requirement for Notch signaling in lung oncogenesis, crossing the LSL-KRAS(G12D) mouse model with a transgenic with a similarly inducible global dominant-negative suppressor of Notch activity, LSL-DNMAML (dominant-negative mastermind-like), reveals no evidence of Notch pathway requirement for lung tumor initiation or growth in vivo.
Moreover, Klf5 is not required for lung tumor formation in an inducible oncogenic K-Ras(G12D) mouse model of lung tumorigenesis, and non-small cell lung cancer patients expressing high levels of KLF5 (21/258) have a significantly better disease-specific survival than those with intermediate to no KLF5 expression.