共查询到20条相似文献,搜索用时 31 毫秒
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Cinghu S Goh YM Oh BC Lee YS Lee OJ Devaraj H Bae SC 《Journal of cellular physiology》2012,227(3):1071-1080
As H. pylori infection progresses, intestinal metaplasia (IM), a key event in gastric carcinogenesis, develops in the stomach. The mechanism by which H. pylori infection causes the trans-differentiation of gastric cells to intestinal-type cells remains an important question. In the current study, we found that RUNX3 is deregulated in all human IM specimens examined by either down regulation or mislocalization; Aberrant localization of a gastric tumor suppressor RUNX3 is observed in most human cases of IM with concurrent H. pylori infection, and RUNX3 is down-regulated in most cases of IM without H. pylori-infection. The cytoplasmic mislocalization of a RUNX3 was associated with H. pylori-induced c-Src activation and RUNX tyrosine phosphorylation. Moreover, gastric epithelial cells of Runx3(-/-) mice expressed the intestinal markers Muc2 and Li-Cadherin, which suggests that the deregulation of Runx3 is a key event in the intestinalization of the gastric epithelium. Collectively, the results of the current study suggest that RUNX3 deregulation is associated with H. pylori-induced pathogenesis and the development of IM. 相似文献
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RUNX3 suppresses gastric epithelial cell growth by inducing p21(WAF1/Cip1) expression in cooperation with transforming growth factor {beta}-activated SMAD 总被引:3,自引:0,他引:3 下载免费PDF全文
Chi XZ Yang JO Lee KY Ito K Sakakura C Li QL Kim HR Cha EJ Lee YH Kaneda A Ushijima T Kim WJ Ito Y Bae SC 《Molecular and cellular biology》2005,25(18):8097-8107
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Chen LF 《Journal of cellular biochemistry》2012,113(5):1470-1477
Emerging evidence indicates that RUNX3 is a tumor suppressor in breast cancer. RUNX3 is frequently inactivated in human breast cancer cell lines and cancer samples by hemizygous deletion of the Runx3 gene, hypermethylation of the Runx3 promoter, or cytoplasmic sequestration of RUNX3 protein. Inactivation of RUNX3 is associated with the initiation and progression of breast cancer. Female Runx3(+/-) mice spontaneously develop ductal carcinoma, and overexpression of RUNX3 inhibits the proliferation, tumorigenic potential, and invasiveness of breast cancer cells. This review is intended to summarize these findings and discuss the tumor suppressor function of RUNX3 in breast cancer. 相似文献
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Fukamachi H 《Development, growth & differentiation》2006,48(1):1-13
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RUNX3 cooperates with FoxO3a to induce apoptosis in gastric cancer cells 总被引:12,自引:0,他引:12
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Upstream and downstream targets of RUNX proteins 总被引:23,自引:0,他引:23
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Laura McDonald Nicola Ferrari Anne Terry Margaret Bell Zahra M. Mohammed Clare Orange Alma Jenkins William J. Muller Barry A. Gusterson James C. Neil Joanne Edwards Joanna S. Morris Ewan R. Cameron Karen Blyth 《Disease models & mechanisms》2014,7(5):525-534
RUNX2, a master regulator of osteogenesis, is oncogenic in the lymphoid lineage; however, little is known about its role in epithelial cancers. Upregulation of RUNX2 in cell lines correlates with increased invasiveness and the capacity to form osteolytic disease in models of breast and prostate cancer. However, most studies have analysed the effects of this gene in a limited number of cell lines and its role in primary breast cancer has not been resolved. Using a human tumour tissue microarray, we show that high RUNX2 expression is significantly associated with oestrogen receptor (ER)/progesterone receptor (PR)/HER2-negative breast cancers and that patients with high RUNX2 expression have a poorer survival rate than those with negative or low expression. We confirm RUNX2 as a gene that has a potentially important functional role in triple-negative breast cancer. To investigate the role of this gene in breast cancer, we made a transgenic model in which Runx2 is specifically expressed in murine mammary epithelium under the control of the mouse mammary tumour virus (MMTV) promoter. We show that ectopic Runx2 perturbs normal development in pubertal and lactating animals, delaying ductal elongation and inhibiting lobular alveolar differentiation. We also show that the Runx2 transgene elicits age-related, pre-neoplastic changes in the mammary epithelium of older transgenic animals, suggesting that elevated RUNX2 expression renders such tissue more susceptible to oncogenic changes and providing further evidence that this gene might have an important, context-dependent role in breast cancer.KEY WORDS: RUNX2, Breast cancer, Transgenic model, Mammary development 相似文献
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Liu Z Xu X Chen L Li W Sun Y Zeng J Yu H Chen C Jia J 《Journal of cellular biochemistry》2012,113(3):1080-1086
Infection with CagA-positive Helicobacter pylori is the strongest risk factor for gastric carcinoma. Upon delivery into gastric epithelial cells, CagA disturbs cellular functions by physically interacting with and deregulating intracellular signaling molecules via both tyrosine phosphorylation-dependent and -independent mechanisms. Runx3 was suggested to be a tumor suppressor and closely associated with tumorigenesis and progression of gastric cancer. The aim of our study is to verify the effect of H. pylori virulence factor CagA on Runx3 expression level and investigate the corresponding molecular mechanisms and signaling pathways influencing Runx3 expression. Human gastric epithelial immortalized GES-1 cells were transfected with CagA-expression vector or control vector with FuGENE HD transfection reagent. Runx3 expression levels were determined by QRT-PCR and immunoblotting. Then we constructed a 1,150 bp Runx3 promoter luciferase reporter plasmid, pGL(3)-1150 bp, which was co-transfected into GES-1 cell with CagA-expression vector or control vector. Luciferase reporter assay was used to determine the effects of CagA on the 1,150 bp promoter activity of Runx3. Signal inhibitors were used to detect the signal pathway(s) through which CagA affects Runx3. Our results showed that CagA can reduce the expression level of Runx3 at both mRNA and protein levels significantly. Importantly, the 1,150 bp Runx3 promoter activity was decreased in cells transfected with CagA-expression vector comparing with cells transfected with control vector. And this inhibition is dependent on the phosphorylation of CagA. Signal pathways Src/MEK/ERK and p38 MAPK are involved in this regulation. Our findings provide new insights for understanding the mechanism of H. pylori carcinogenesis. 相似文献
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The RUNX3 gene--sequence, structure and regulated expression. 总被引:38,自引:0,他引:38
C Bangsow N Rubins G Glusman Y Bernstein V Negreanu D Goldenberg J Lotem E Ben-Asher D Lancet D Levanon Y Groner 《Gene》2001,279(2):221-232
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Runx1 is required for zebrafish blood and vessel development and expression of a human RUNX1-CBF2T1 transgene advances a model for studies of leukemogenesis 总被引:11,自引:0,他引:11
Kalev-Zylinska ML Horsfield JA Flores MV Postlethwait JH Vitas MR Baas AM Crosier PS Crosier KE 《Development (Cambridge, England)》2002,129(8):2015-2030