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. Author manuscript; available in PMC: 2015 Jul 3.
Published in final edited form as: Cell. 2014 Jun 19;158(1):171–184. doi: 10.1016/j.cell.2014.06.004

Figure 7. Yap1 activity is required for endogenously acquired KRAS resistance in vivo.

Figure 7

(A) Schematic of mouse transplant model of KRAS-driven lung cancer. KrasG12D;p53fl/fl lung adenocarcinoma cells were infected with retroviral vectors expressing rtTA3, luciferase and a tet-on shKras. Cells were transplanted into recipient mice by tail vein injection. 7 d later, mice were fed a doxycycline diet to induce shKras in tumor cells (D0). (B) Time course of tumor regression and relapse after Kras suppression. Mean ± SD shown. N=3 off dox and N=10 on dox. (C) Suppression of Kras in tumor tissue. Kras mRNA was measured by qRT-PCR in microdissected lung tumors after the indicated days of doxycycline treatment. (D) Enrichment of a published YAP1 signature (Dupont et al., 2011) after 21 d doxycycline treatment versus untreated cells. (E) Enrichment of a published EMT signature (Taube et al., 2010) after 21 d doxycycline treatment versus untreated cells. (F) Yap1 localization in tumors that escape Kras suppression. Immunohistochemistry was performed with Yap1 antibody on frozen tissue sections from tumors which developed after Kras suppression (dox on) for 21 d and tumors which formed with continued Kras expression (dox off). (G) Tumor response to suppression of Kras in combination with Yap1 or control suppression. Mean ± SD shown. See also Figure S7 and Table S5.