RASAL1 Attenuates Gastric Carcinogenesis in Nude Mice by Blocking RAS/ERK Signaling

Abstract

Recent studies have suggested that the RAS protein activator like-1 (RASAL1) functions as a tumor suppressorin vitro and may play an important role in the development of gastric cancer. However, whether or not RASAL1suppresses tumor growth in vivo remains to be determined. In the present study, we investigated the role ofRASAL1 in gastric carcinogenesis using an in vivo xenograft model. A lentiviral RASAL1 expression vector wasconstructed and utilized to transfect the human poorly differentiated gastric adenocarcinoma cell line, BGC-823.RASAL1 expression levels were verified by quantitative real-time RT-PCR and Western blotting analysis. Then,we established the nude mice xenograft model using BGC-823 cells either over-expressing RASAL1 or normal.After three weeks, the results showed that the over-expression of RASAL1 led to a significant reduction in bothtumor volume and weight compared with the other two control groups. Furthermore, in xenograft tissues theincreased expression of RASAL1 in BGC-823 cells caused decreased expression of p-ERK1/2, a downstreammoleculein the RAS/RAF/MEK/ERK signal pathway. These findings demonstrated that the over-expression ofRASAL1 could inhibit the growth of gastric cancer by inactivation of the RAS/RAF/MEK/ERK pathway invivo. This study indicates that RASAL1 may attenuate gastric carcinogenesis.