Kirsten rat sarcoma virus (KRAS) mutation is considered to be the event that leads to the initiation of pancreatic ductal adenocarcinoma (PDAC), the mutation frequency of the KRAS gene in PDAC is 90‑95%. Studies have shown that wild‑type KRAS (KRASWT) has a survival advantage in PDAC and can antagonize the effect of mutated KRAS G12D (KRASG12D), leading to a low cell transformation efficiency. The present study focused on the differences in biological behavior between KRASWT and KRASG12D and explored the mechanism in pancreatic cancer. Overexpressed KRASWT and KRASG12D was transfected into cells through lentiviral transfection. The differences and mechanisms were explored using cell counting kit‑8 (CCK‑8), clone formation, wound healing and Transwell assays, as well as western blotting, immunohistochemistry and tumor formation in nude mice. In vitro, the proliferation of KRASWT group was reduced compared with PANC‑1 group, while the proliferation of KRASG12D group was not significantly changed. In vivo, the proliferation of KRASWT group was reduced and that of KRASG12D group was enhanced compared with that in the PANC‑1 group. The invasion and migration of KRASWT group were decreased, while the invasion and migration of KRASG12D group were increased. Western blotting showed that the expression of E‑cadherin, α‑E‑catenin, MMP‑3, MMP‑9, STAT3 and phosphorylated STAT3 in KRASWT group was increased, while no significant difference was observed in KRASG12D group. The results of immunohistochemistry were consistent with those of western blotting. KRASWT group can inhibit the proliferation of pancreatic cancer in vitro and in vivo, while KRASG12D group can significantly promote proliferation in vivo, but not significantly in vitro. Wild‑type KRAS may inhibit the invasion and migration of pancreatic cancer through the Wnt/β‑catenin pathway.
Keywords: Wnt/β‑catenin; mutant Kirsten rat sarcoma virus; pancreatic cancer; wild‑type Kirsten rat sarcoma virus.