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. Author manuscript; available in PMC: 2018 Sep 22.
Published in final edited form as: Oncogene. 2018 Mar 22;37(26):3528–3548. doi: 10.1038/s41388-018-0190-7

Figure 8.

Figure 8

AMPKα2, CaMKKβ and p-C/EBPβ levels are markedly decreased in KRASG12D- and BRAFV600E-driven mouse lung tumors. (a) H&E stained lung areas from a normal WT mouse, a KrasLA2/+ mouse45 containing adenocarcinomas (ADC) and a LSL-BRAFV600E/+ animal46 bearing multiple adenomas. (b) Normal and lung tumor areas from a 165 day-old KrasLA2/+ mouse; sections were immunostained for AMPKα2, CaMKKβ, p-C/EBPβ (Thr188) and total C/EBPβ. (c) Normal and lung tumor areas from a 190 day-old LSL-BRAFV600E/+ animal (103 days after intratracheal instillation of Ad.Cre virus); sections were immunostained for AMPKα2, CaMKKβ, p-C/EBPβ (Thr188) and total C/EBPβ. (d) Model depicting AMPK-dependent pathways that mediate C/EBPβ activation and senescence in response to energy stress/AMPK agonists or oncogenic RAS. AMPK signaling suppresses the UPA mechanism that inhibits C/EBPβ activation and thus licenses C/EBPβ activation. To become activated, C/EBPβ also requires signaling through the RAS-ERK cascade to induce phosphorylation on Thr188 as well as other modifications5,62.