Figure 6: Sos-mediated cross-activation of WT Ras by oncogenic K-Ras is required for tumour growth.

(a) MIA PaCa-2 cells harbouring the indicated inducible constructs were injected subcutenously into mice. Following injections, animals were fed doxycycline-containing diet and tumour growth was measured as described in Methods. Values are means±s.d. from three independent experiments. (b) Representative mice and tumours are shown. (c) Signalling analysis of the indicated xenografts. ERK activity was assessed by immunoblotting for pERK and K-Ras-GTP levels were determined by RBD pull down. Tubulin was used as a loading control. (d) Values of ERK activity are presented as fold activation compared with shCtrl and represent means±s.d. from three independent experiments. (e) Cell proliferation of the indicated xenografts as assessed by immunohistochemical staining for Ki-67. Images shown are representative of three independent experiments. Scale bars, 50 μm. (f) Schematic depiction of the role of Sos in oncogenic Ras-driven tumorigenesis. The binding of oncogenic Ras (Onc.) to the allosteric site promotes the activation of WT Ras. The signalling output of both forms of Ras is required for tumorigenesis.