Runx3/Pebp2alphaC null mouse gastric mucosa exhibits hyperplasias due to stimulated proliferation and suppressed apoptosis in epithelial cells, and the cells are resistant to growth-inhibitory and apoptosis-inducing action of TGF-beta, indicating that Runx3 is a major growth regulator of gastric epithelial cells. Between 45% and 60% of human gastric cancer cells do not significantly express RUNX3 due to hemizygous deletion and hypermethylation of the RUNX3 promoter region. Tumorigenicity of human gastric cancer cell lines in nude mice was inversely related to their level of RUNX3 expression, and a mutation (R122C) occurring within the conserved Runt domain abolished the tumor-suppressive effect of RUNX3, suggesting that a lack of RUNX3 function is causally related to the genesis and progression of human gastric cancer.

Highlights d The SLC1A5 variant is a mitochondrial glutamine transporter d The SLC1A5 variant has a mitochondrial targeting sequence d Hypoxia controls SLC1A5 variant expression through HIF-2a d The SLC1A5 variant mediates mitochondrial glutamine metabolism in cancer

In this study, we show that the formation of polyploidy following sustained mitotic checkpoint activation appears to be preceded by the ubiquitin-dependent proteolysis of hBubR1. In addition, the level of hBubR1 is significantly reduced not only in polyploid cells created by sustained mitotic spindle damage, but also in 21 (31.3%) of 67 human colon adenocarcinomas tested. Importantly, the introduction of hBubR1 triggers the apoptosis of polyploid cells formed by aberrant exit from mitosis and inhibits the growth of tumors established with these cells in athymic nude mice. These results suggest that hBubR1-mediated apoptosis prevents the propagation of cells that breach the mitotic checkpoint and that the control of hBubR1 protein level is an important factor in the acquisition of preneoplastic polyploidy.

PJJ. 2010. Developmental phytotoxicity of metal oxide nanoparticles to Arabidopsis thaliana. Environ Toxicol Chem 29:669-675.