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

Neoplasia. Jan-Feb 2001;3(1):4-9. doi: 10.1038/sj.neo.7900132.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Amino Acid Sequence
  • Axin Protein
  • Blotting, Northern
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cytoskeletal Proteins / metabolism
  • DNA Primers / chemistry
  • Genes, APC / genetics
  • Genes, APC / physiology
  • Genetic Vectors
  • Humans
  • Immunoenzyme Techniques
  • Lac Operon / physiology
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Molecular Sequence Data
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / isolation & purification*
  • Neoplasm Proteins / metabolism
  • Oligonucleotide Array Sequence Analysis / methods
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / isolation & purification*
  • Protein-Serine-Threonine Kinases / metabolism
  • Proteins / genetics
  • Proteins / metabolism
  • Recombinant Proteins / metabolism
  • Repressor Proteins*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • TCF Transcription Factors
  • Trans-Activators*
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transfection
  • Tumor Cells, Cultured
  • beta Catenin

Substances

  • Axin Protein
  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • DNA Primers
  • Neoplasm Proteins
  • Proteins
  • Recombinant Proteins
  • Repressor Proteins
  • TCF Transcription Factors
  • TCF7L2 protein, human
  • Trans-Activators
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors
  • beta Catenin
  • MARK1 protein, human
  • MARK3 protein, human
  • Protein-Serine-Threonine Kinases