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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-7-28
pubmed:abstractText
Transforming growth factor-beta1 (TGF-beta1) is a multi-functional cytokine involved in the regulation of cell proliferation, differentiation and extracellular matrix formation. In search for novel genes mediating the TGF-beta1 function at downstream signaling, we performed a cDNA microarray analysis and identified 60 genes whose expression is regulated by TGF-beta1 in the liver cancer cell line PLC/PRF/5. Among them, we report here lysyl oxidase like 4 (LOXL4) as a novel target of TGF-beta1 signaling, and provide experimental evidence for its expression regulation and function. LOXL4 was found to be the only member of LOX family whose expression is induced by TGF-beta1 in hepatoma cells. Deletion mapping of the LOXL4 promoter indicated that the TGF-beta1 regulation of LOXL4 expression is mediated through the binding of AP1 transcription factor to a conserved region of the promoter. This was confirmed by the chromatin immunoprecipitation assay that captured c-Fos-bound chromatin from TGF-beta1-treated cells. Forced expression of LOXL4 in PLC/PRF/5 cells resulted in inhibition of cell motility through Matrigel in the presence of TGF-beta1 treatment. In parallel, LOXL4 suppressed the expression of laminins and alpha3 integrin and the activity of MMP2. These results suggest that LOXL4 may function as a negative feedback regulator of TGF-beta1 in cell invasion by inhibiting the metabolism of extracellular matrix (ECM) components.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1090-2104
pubmed:author
pubmed:issnType
Electronic
pubmed:day
5
pubmed:volume
373
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
521-7
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18586005-Amino Acid Oxidoreductases, pubmed-meshheading:18586005-Carcinoma, Hepatocellular, pubmed-meshheading:18586005-Cell Line, Tumor, pubmed-meshheading:18586005-Cell Movement, pubmed-meshheading:18586005-Extracellular Matrix, pubmed-meshheading:18586005-Feedback, Physiological, pubmed-meshheading:18586005-Gene Expression Regulation, Enzymologic, pubmed-meshheading:18586005-Gene Expression Regulation, Neoplastic, pubmed-meshheading:18586005-Humans, pubmed-meshheading:18586005-Liver Neoplasms, pubmed-meshheading:18586005-Neoplasm Invasiveness, pubmed-meshheading:18586005-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:18586005-Transcription, Genetic, pubmed-meshheading:18586005-Transcription Factor AP-1, pubmed-meshheading:18586005-Transforming Growth Factor beta1
pubmed:year
2008
pubmed:articleTitle
Lysyl oxidase like 4, a novel target gene of TGF-beta1 signaling, can negatively regulate TGF-beta1-induced cell motility in PLC/PRF/5 hepatoma cells.
pubmed:affiliation
Medical Genomics Research Center, KRIBB, P.O. Box 115, Yusong, Daejeon 305-806, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't