K15 Promoter-Driven Enforced Expression of NKIRAS Exhibits Tumor Suppressive Activity Against the Development of DMBA/TPA-Induced Skin Tumors
October 2021
in “
Scientific Reports
”
TLDR NKIRAS2 can suppress certain skin tumors but its effect on cancer varies with context and expression level.
The study investigated the role of NKIRAS2 in carcinogenesis using transgenic mice with enforced expression of NKIRAS2 driven by a K15 promoter, primarily active in follicle bulge cells. The results showed that NKIRAS2 expression did not affect epidermal development but effectively suppressed DMBA/TPA-induced skin tumors, indicating a tumor suppressive role in follicle bulges. However, in murine fibroblasts, NKIRAS2 was necessary for HRAS-mutant-driven cellular transformation, with moderate expression enhancing and excessive expression suppressing oncogenic activity. This suggested that NKIRAS2's role in cancer is influenced by cellular context and expression level, exhibiting a biphasic effect on HRAS-driven oncogenesis.
