Abstract
Recent studies have suggested that the RAS protein activator like-1 (RASAL1) functions as a tumor suppressor in vitro and may play an important role in the development of gastric cancer. However, whether or not RASAL1 suppresses tumor growth in vivo remains to be determined. In the present study, we investigated the role of RASAL1 in gastric carcinogenesis using an in vivo xenograft model. A lentiviral RASAL1 expression vector was constructed 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 both tumor volume and weight compared with the other two control groups. Furthermore, in xenograft tissues the increased expression of RASAL1 in BGC-823 cells caused decreased expression of p-ERK1/2, a downstream moleculein the RAS/RAF/MEK/ERK signal pathway. These findings demonstrated that the over-expression of RASAL1 could inhibit the growth of gastric cancer by inactivation of the RAS/RAF/MEK/ERK pathway in vivo. This study indicates that RASAL1 may attenuate gastric carcinogenesis.
Highlights
The RAS proteins control signaling pathways that are key regulators of several aspects of normal cell growth and malignant transformation
Consistent with the mRNA level, there was a significant increase in the protein levels (Figure 1A, C) of RAS protein activator like-1 (RASAL1) in the BGC-823-RASAL1 cells compared to the parental BGC-823 and BGC-823NC cell line
Overexpresion of RASAL1 suppresses tumor growth in vivo To explore the effects of RASAL1 on gastric cancer in vivo, we established a xenograft model
Summary
The RAS proteins control signaling pathways that are key regulators of several aspects of normal cell growth and malignant transformation. RAS mutations at hot spots, such as G12 and Q61, which is insensitive to RAS GAPs, result in a slower GTPhydrolysis rate that leads to longer activated signaling pathways promoting uncontrolled cell growth and are responsible for over 25% of human tumors (Karnoub et al, 2008; Lu et al, 2011). Reactivation of RASAL1, DAB2IP, and PITX1 inhibited proliferation and induced apoptosis, whereas their silencing increased proliferation and resistance to apoptosis. They supposed that RAS GAPs may emerge as a class of tumor suppressors and provide a novel mechanism of activating RAS signaling pathway
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