Isolation of a novel human gene, MARKL1, homologous to MARK3 and its involvement in hepatocellular carcinogenesis

Activation of the Wnt-signaling pathway is known to play a crucial role in carcinogenesis of various human organs including the colon, liver, prostate , and endometrium, To investigate the mechanisms underlying hepatocellular carcinogenesis, we attempted to identify genes regulated by beta -catenin/T cf complex in a human hepatoma cell line, HepG2, in which an activated form of beta -catenin is expressed, By means of cDNA microarray, we isolated a novel human gene, termed MARKL1 (MAP/microtubule affinity-regulating kinase -like 1), whose expression was downregulated in response to decreased Tcf/L EF1 activity, The transcript expressed in liver consisted of 3529 nucleotid es that contained an open reading frame of 2256 nucleotides, encoding 752 a mino acids homologous to human MARKS (MAP/ microtubule affinity-regulating kinase 3), Expression levels of MARKL1 were markedly elevated in eight of n ine HCCs in which nuclear accumulation of beta -catenin was observed, which may suggest that MARKL1 plays some role in hepatocellular carcinogenesis.