International Journal of Molecular Medical Science, 2024, Vol.14, No.5, 305-314 http://medscipublisher.com/index.php/ijmms 310 5). This case underscores the potential of developing next-generation inhibitors that can target specific resistance mutations and highlights the importance of personalized treatment strategies in managing resistance in pancreatic cancer patients. Figure 3 KRAS is dispensable for in vitro and in vivo proliferation of PDAC cells (Adopted from Muzumdar et al., 2017) Image caption: a) Western blot confirmed loss of KRAS protein in knockout clones (A13-K1,K2, 8988T-H9,H36) compared to intact clones (A13-E1,E2, 8988T E3, E6). HSP90 is loading control. b) RAS-GTP levels were decreased in knockout (8988T-H9 and A13-K1, K2) compared to intact (8988T E3 and A13-E1,E2) clones. GTPγS (non-hydrolysable)-treated positive control (GTP PD) and GDP-treated negative control (GDP PD) for 8988T E3 are shown. PD pull-down. Inp input before pull-down. c) KRAS deficient clones exhibited altered cell morphology, characterized by increased cell size, cytoplasmic translucency, and smooth edges. Scale bar is 100 µm. d) KRAS deficient clones showed diminished anchorage-independent growth in soft agar. Scale bar is 500 µm. e) Growth curves for A13 and 8988T KRAS intact and deficient (KO) clones. Average cell viability (normalized to day 0) ± s.e.m. is plotted for A13 (n = 2 clones) and 8988T (n = 4 clones). f) A13, 8988T, and PANC-1 clones exhibited comparable efficiency generating tumors following subcutaneous transplant in nude mice regardless of KRAS status. Shown are cumulative data from two KRAS intact and two deficient clones for A13 and 8988T and one intact and one deficient clone for PANC-1. g) A13 KRAS deficient tumors grew at a slower rate than intact tumors. Average tumor volume fold increase (normalized to day 0 when tumors were ~0.5 cm in diameter) ± s.e.m. is plotted (n = 8 tumors per group) (Adopted from Muzumdar et al., 2017)
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