Activated K-RAS and its effect on morphological appearance.

RAS genes are frequently mutated in various human tumours. These mutations cause GTPase RAS to remain locked in constitutively active signals through the downstream cascades leading to proliferation. A series of earlier studies reported on the morphological appearance of cells upon RAS activation. Classically, morphologic changes of fibroblasts have been used to confirm the oncogenic activity of RAS. Recent works found that the active RAS induces benign and malignant morphological changes in organoids, which are an in vitro model system for epithelial tissue. The studies of animal models support the basic oncogenic features of RAS revealed in vitro, while also providing evidence that the effects of RAS activation in vivo are different from those in vitro. The pathological observation of the various human materials indicates that the oncogenic RAS participates in metaplasia, which occurs before proliferation, and that RAS promotes mucin production in various organs. These morphological analyses may shed light on important signalling pathways that merit investigation in vitro.