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/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.
Kato
T
T
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Satoh
S
S
Okabe
H
H
Kitahara
O
O
Ono
K
K
Kihara
C
C
Tanaka
T
T
Tsunoda
T
T
Yamaoka
Y
Y
Nakamura
Y
Y
Furukawa
Y
Y
D000256:Adenoviridae / Q000235:genetics; D000595:Amino Acid Sequence; D060466:Axin Protein; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D017491:Genes, APC / Q000235:genetics / Q000502:physiology; D005822:Genetic Vectors; D006801:Humans; D007124:Immunoenzyme Techniques; D007763:Lac Operon / Q000502:physiology; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D051820:TCF Transcription Factors; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D051176:beta Catenin
D060466:Axin Protein; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D009363:Neoplasm Proteins; D011506:Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D051176:beta Catenin; C105547:MARK1 protein, human; C111833:MARK3 protein, human; D017346:Protein Serine-Threonine Kinases