Extended Data Fig. 9: MPMs may be caused by hyperactivation of the NHE1/cyclin D1 axis.
From: Cytosolic pH regulates proliferation and tumour growth by promoting expression of cyclin D1
(a) MPMs are associated with high CDK4cyclin D activity. Percentage of patients with the indicated mutations was determined from 2 patient cohorts as described in Materials and Methods. Only mutations in genes linked to the cyclin D/RB pathway are shown. (b) Cells were grown and treated as in Fig. 4c and cyclin D1 protein abundance was analyzed by western blot. Blots representative of three independent experiments are shown. (c) Cells were grown and phosphorylation of RB was analyzed upon DMA treatment (mean ± SEM of independent experiments, N=4). Scale bar represents 100 µm. (d) Cells subjected to siRNA mediated knockdown of NHE1 and cyclin D1 and NHE1 protein levels were analyzed by western blot (mean ± S.E.M. of 3 independent experiments). (e) NHE1 is the most abundant NHE isoform in MPM cell lines. Steady state mRNA levels of the indicated genes relative to NHE1 were determined by qPCR (mean ± SEM of independent experiments, N=3).
