| First Author | Sakai T | Year | 2010 |
| Journal | Int J Cancer | Volume | 126 |
| Issue | 5 | Pages | 1079-94 |
| PubMed ID | 19637241 | Mgi Jnum | J:157049 |
| Mgi Id | MGI:4429781 | Doi | 10.1002/ijc.24789 |
| Citation | Sakai T, et al. (2010) Inflammatory disease and cancer with a decrease in Kupffer cell numbers in Nucling-knockout mice. Int J Cancer 126(5):1079-94 |
| abstractText | Nucling is a stress-inducible protein associated with apoptosomes. The cytochrome c-triggered formation of apoptosomes represents a key-initiating event in apoptosis. We have recently reported that Nucling regulates the apoptotic pathway by controlling the activation of NF-kappaB as well. Here we show that hepatocellular carcinoma (HCC) arising spontaneously against a background of hepatitis occurred more frequently in Nucling-knockout (KO) mice than wild-type (WT) mice. Biochemical serum testing revealed potential liver dysfunction with hypercholesterolemia in Nucling-KO males. In the background of Nucling-KO mice, we observed the up-regulation of TNFalpha, spontaneous NF-kappaB-activation and the induction of galectin-3 expression in liver. In addition, we observed a decrease in the number of Kupffer cells (KCs) in the KO mice. KCs are important for the hepatic immune system, acting as phagocytes or antigen-presenting cells (APCs). We found that KCs in Nucling-KO mice were apoptotic possibly through the up-regulation of TNFalpha. These observations indicate that Nucling is important for the regulation of NF-kappaB signals in liver. We propose that Nucling deficiency could be a powerful tool to reveal the NF-kappaB-related molecular networks leading to hepatitis and HCC development. |
