AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1

The Wnt signaling pathway is essential for development and organogenesis. Wnt signaling stabilizes beta-catenin, which accumulates in the cytoplasm, binds to 1-cell factor (TCF; also known as lymphocyte enhancer-binding factor, LEF) and then upregulates downstream genes. Mutations in CTNNB1 (encoding beta-catenin) or APC (adenomatous polyposis coli) have been reported in human neoplasms including colon cancers and hepatocellular carcinomas (HCCs). Because HCC5 tend to show accumulation of beta-catenin more often than mutations in CTNNB1, we looked for mutations in AXIN1, encoding a key factor for Wnt signaling, in 6 HCC cell lines and 100 primary HCC5. Among the 4 cell lines and 87 HCC5 in which we did not detect CTNNB1 mutations, we identified AXIN1 mutations in 3 cell lines and 6 mutations in 5 of the primary HCCs. In cell lines containing mutations in either gene, we observed increased DNA binding of TCF associated with beta-catenin in nuclei. Adenovirus mediated gene transfer of wild-type AXINI induced apoptosis in hepatocellular and colorectal cancer cells that had accumulated beta-catenin as a consequence of either APC, CTNNB1 or AXIN1 mutation, suggesting that axin may be an effective therapeutic molecule for suppressing growth of hepatocellular and colorectal cancers.     

一种新型高价锰取代的多金属氧酸盐合成、结构及性质研究

在含有MnⅡ的夹心型多金属氧酸盐水溶液中加入强氧化剂KMnO4,制得一种新型的含有MnⅢ的多金属氧酸盐K5Na3[{MnⅢ(H2O)}2(WO)(H2O) (AsW9O33)2]·18H2O (KNa-1).该化合物的多阴离子结构是基于2个B-α-[AsW9]三缺位Keggin型构筑单元,中间夹着2个{MnⅢ(H2O)}和1个{WⅥO}片段而构成的夹心式构型.对KNa-1进行了变温磁化率测定并采用双核MnⅢ簇为模型进行了拟合,并对该化合物进行了电化学分析.结果表明:KNa-1 中的2个MnⅢ中心存在弱的反铁磁相互作用;化合物中的MnⅢ离子具有不可逆的氧化还原过程.