Abstract
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/Tcf 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/LEF1 activity. The transcript expressed in liver consisted of 3529 nucleotides that contained an open reading frame of 2256 nucleotides, encoding 752 amino acids homologous to human MARK3 (MAP/microtubule affinity-regulating kinase 3). Expression levels of MARKL1 were markedly elevated in eight of nine HCCs in which nuclear accumulation of beta-catenin were observed, which may suggest that MARKL1 plays some role in hepatocellular carcinogenesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoviridae / genetics
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Amino Acid Sequence
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Axin Protein
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Blotting, Northern
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Carcinoma, Hepatocellular / genetics*
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Carcinoma, Hepatocellular / metabolism
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Carcinoma, Hepatocellular / pathology
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Cytoskeletal Proteins / metabolism
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DNA Primers / chemistry
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Genes, APC / genetics
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Genes, APC / physiology
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Genetic Vectors
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Humans
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Immunoenzyme Techniques
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Lac Operon / physiology
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Liver Neoplasms / genetics*
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Liver Neoplasms / metabolism
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Liver Neoplasms / pathology
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Molecular Sequence Data
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Neoplasm Proteins / genetics
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Neoplasm Proteins / isolation & purification*
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Neoplasm Proteins / metabolism
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Oligonucleotide Array Sequence Analysis / methods
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Protein Serine-Threonine Kinases / chemistry
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / isolation & purification*
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Protein Serine-Threonine Kinases / metabolism
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Proteins / genetics
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Proteins / metabolism
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Recombinant Proteins / metabolism
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Repressor Proteins*
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Reverse Transcriptase Polymerase Chain Reaction
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Sequence Homology, Amino Acid
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TCF Transcription Factors
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Trans-Activators*
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Transcription Factor 7-Like 2 Protein
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transfection
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Tumor Cells, Cultured
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beta Catenin
Substances
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Axin Protein
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CTNNB1 protein, human
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Cytoskeletal Proteins
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DNA Primers
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Neoplasm Proteins
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Proteins
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Recombinant Proteins
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Repressor Proteins
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TCF Transcription Factors
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TCF7L2 protein, human
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Trans-Activators
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Transcription Factor 7-Like 2 Protein
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Transcription Factors
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beta Catenin
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MARK1 protein, human
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MARK3 protein, human
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Protein Serine-Threonine Kinases