TI - JNK1 activation in HCC . AB - We had previously shown activation of JNK1 in about 55% of human HCC samples as compared with the case-matched ANC samples through immunoblotting[13] . To validate these observations again , we also examined JNK activation status in some additional HCC tissue samples paired with ANC tissue in tissue microarray through immunohistochemistry ( IHC ) analysis ( Fig 1 ) . Since an antibody specific for PHOSphorylated-JNK1 ( pJNK1 ) was unavailable , we used an antibody against both pJNK1 and pJNK2 . Despite the fact that both HCC and ANC exhibited a similar weak background signal in IHC , possibly due to pJNK2 as demonstrated in our previous Westernblotting[13] , 24 out of 52 HCC samples ( 46% ) in the tissue microarray slides showed a notable enhancement of pJNK signal as compared with the ANC tissue ( representative images in Fig 1A ) . Of note , the enhancement of JNK activation as implicated in the PHOSphorylation of the JNK largely occurred in the nuclei of the hepatocytes ( top panels in Fig 1A ) and was not uniformly distributed in the whole HCC tissue in the majority of tissue slides , but rather , clustered in certain limited areas , especially in those areas featured with small foci of necrosis ( Fig 1B ) . The JNK1 activation was further validated by a JNK1 specific kinase activity assay in additional 4 HCC samples paired with the ANC tissues (Fig 1C) .