期刊
ONCOTARGET
卷 6, 期 29, 页码 28425-28439出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.4952
关键词
NKX6.3; differentiation; cell proliferation; cell death; stomach
资金
- Basic Science Research Program through National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2015R1A2A2A05001023, 2014R1A1A2058693]
- National Research Foundation of Korea [2014R1A1A2058693, 2015R1A2A2A05001023] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
NKX6.3 transcription factor is known to be an important regulator in gastric mucosal epithelial differentiation. The present study aimed to investigate whether NKX6.3 acts as an essential tumor suppressor in gastric carcinogenesis. Absent or reduced protein expression and decreased DNA copy number and mRNA transcript of the NKX6.3 gene were frequently observed in gastric cancers. Overexpression of NKX6.3 in AGS(NKX6.3) and MKN1(NKX6.3) cells markedly arrested cell proliferation by inhibiting cell cycle progression and induced apoptosis through both death receptor-and mitochondrial-pathways. In addition, stable NKX6.3 transfectants increased the expression of gastric differentiation markers, including SOX2 and Muc5ac, and decreased the expression of intestinal differentiation markers, CDX2 and Muc2. In ChIP-cloning and sequencing analyses, NKX6.3 coordinated a repertoire of target genes, some of which are clearly associated with cell cycle, differentiation and death. In particular, NKX6.3 transcriptional factor was found to bind specifically to the upstream sequences of GKN1, a gastric-specific tumor suppressor, and dramatically increase expression of the latter. Furthermore, there was a positive correlation between NKX6.3 and GKN1 expression in non-cancerous gastric mucosae. Thus, these data suggest that NKX6.3 may control the fate of gastric mucosal cells and function as a gastric tumor suppressor.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据