Extended Data Fig. 8: Oncogenic KRAS induces the expression of OAT and polyamine synthesis genes.

a, mRNA levels of Srm, Sms and Arg2 in iKras cell lines #1 and #2 maintained in Dox (1μg ml⁻¹) for 24 h prior to Dox deprivation for 24, 48, or 72 h. n = 3 biological replicates. b,c, mRNA levels of KRAS, OAT, ODC1, SRM, SMS and ARG2 in human PDA AsPC-1 (b) or MIA PaCa-2 (c) cells with Dox-inducible knockdown of GFP (Tet on-shGFP) or KRAS (Tet on-shKRAS hairpins #1 and #2) that were cultured in Dox (1μg ml⁻¹) for 24, 48 or 72 h. In b, n = 3 and in c, n =2 biological replicates. d, mRNA levels of ornithine and polyamine synthesis genes (OAT, ODC1, SRM, SMS and ARG2) in AsPC-1 and MIA PaCa-2 cells treated with vehicle control DMSO or inhibitors of: PI3K (BKM 120, 150 nM); AKT (MK2206, 200 nM); MEK (AZD6244, 50 nM); mTORC1 (Rapamycin, 20 nM) for 72 h. n = 3 biological replicates. Data represent the mean ± s.d. (a,b,d) of biological replicates from 3 independent experiments or the mean of biological replicates from 2 independent experiments (c). p-values were obtained by two-way (a,b) or one-way (d) ANOVA followed by Tukey test. Statistical significance is for Off Dox vs. On Dox (a) or for shKRAS vs. shGFP (b) at each indicated time, or for each inhibitor vs. DMSO (d). e, Levels of proteins in cells from d. β-Actin was used as loading control and data represent two independent experiments.