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following the production of lentiviruses, hpde or a13 cells were infected by infection efficiency was measured. for in vitro experiments, infection efficiency was between 70 and 80 %, as estimated by green fluorescent protein (gfp) expression. for in vivo experiments, cells were cloned by limiting dilution and the ratio of gfp-positive cells to total cells was greater than 98 %. hpde or a13 cells were collected for qpcr and western blot analysis to detect ectopic kras expression. for in vivo experiment, human pdac cell lines (a13 and 990p) were infected with lenti- kras-gfp before subcutaneous transplantation. after intratumoral administration of dox for 4 weeks, mice were euthanized to examine tumor growth. (supplemenatary fig. 3a). mice were monitored daily and tumor sizes were measured and recorded as a length (l) x width (w) x width (h) (mm)3. tumor volumes were calculated using the formula: volume = (l x w x h) x 0.5. at the end of the experiment, the mice were euthanized. tumors were photographed, weighed, snap-frozen, and stored at -80 c. tumors were sectioned for immunohistochemical and western blot analyses. immunohistochemistry was performed using monoclonal antibodies against gfp (santa cruz biotechnology, santa cruz, ca), (1:200, 3 hours at 37c), followed by visualization with a goat anti-rabbit secondary antibody (1:400, vector laboratories, burlingame, ca). tissue sections were then stained with hematoxylin and eosin (h&e). results were confirmed in three independent experiments, and representative images are shown.

for the purpose of stable clone establishment, pmaxgfp vectors were co-transfected with the lenti- kras-gfp vector in hek293t cells with a selectable puromycin resistance marker using lipofectamine 2000 (invitrogen). stable cell lines were maintained with 3 mg/ml puromycin (life technologies).

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