In  vivo effects of mutant RHOA on tumor formation in an orthotopic inoculation model.

In vivo effects of mutant RHOA on tumor formation in an orthotopic inoculation model. Oncol Rep. 2019 Sep 03;: Authors: Nishizawa T, Nakano K, Fujii E, Komura D, Kuroiwa Y, Ishimaru C, Monnai M, Aburatani H, Ishikawa S, Suzuki M Abstract Ras homolog family member A (RHOA) mutations are driver genes in diffuse‑type gastric cancers (DGCs), and we previously revealed that RHOA mutations contribute to cancer cell survival and cell migration through their dominant negative effect on Rho‑associated kinase (ROCK) signaling in vitro. However, how RHOA mutations contribute to DGC development in vivo is poorly understood. In the present study, the contribution of RHOA mutations to tumor morphology was investigated using an orthotopic xenograft model using the gastric cancer cell line MKN74, in which wild‑type (WT) or mutated (Y42C and Y42S) RHOA had been introduced. When we conducted RNA sequencing to distinguish between the genes expressed in human tumor tissues from those in mouse stroma, the expression profiles of the tumors were clearly divided into a Y42C/Y42S group and a mock/WT group. Through gene set enrichment analysis, it was revealed that inflammation‑ and hypoxia‑related pathways were enriched in the mock/WT tumors; however, cell metabolism‑ and cell cycle‑related pathways such as Myc, E2F, oxidative phosphorylation and G2M checkpoint were enriched in the Y42C/Y42S tumors. In addition, the gene set related to ROCK ...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research