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Latent transforming growth factor β-binding protein 4 is downregulated in esophageal cancer via promoter methylation
- Source :
- PLoS ONE, Vol 8, Iss 5, p e65614 (2013), PLoS ONE
- Publication Year :
- 2013
- Publisher :
- Public Library of Science (PLoS), 2013.
-
Abstract
- Latent transforming growth factor β-binding protein 4 (LTBP4) is an extracellular matrix molecule that is a member of important connective tissue networks and is needed for the correct folding and the secretion of TGF-β1. LTBP4 is downregulated in carcinomas of various tissues. Here we show that LTBP4 is also downregulated in adenocarcinomas and squamous cell carcinomas of the esophagus in vitro and in vivo. Re-expression of LTBP4 in esophageal cancer cell lines reduced cell migration ability, whereas cell viability and cell proliferation remained unchanged. Hypermethylation of the promoter regions of the two main human LTBP4 transcriptional forms, LTBP4L and LTBP4S, was found to be involved in LTBP4 silencing. Detailed investigations of the methylation patterns of the promoter regions of LTBP4L and LTBP4S identified GATA1, SP1, E2F4 and SMAD3 as potential transcription factors involved in LTBP4 expression. In in vitro transcription factor activity studies we discovered E2F4 as novel powerful regulator for LTBP4S expression.
- Subjects :
- Esophageal Neoplasms
Biochemistry
Molecular cell biology
Cell Movement
Gene Order
Promoter Regions, Genetic
E2F4
Multidisciplinary
GATA1
Extracellular Matrix
Gene Expression Regulation, Neoplastic
Cell Motility
Latent TGF-beta binding protein
Oncology
DNA methylation
Azacitidine
Disease Progression
Medicine
Epigenetics
DNA modification
Protein Binding
Research Article
Esophageal Cancer
Science
Biophysics
Down-Regulation
Biology
Decitabine
Cell Growth
Transforming Growth Factor beta1
Molecular Genetics
Cell Line, Tumor
Gastrointestinal Tumors
Genetics
Humans
Gene silencing
Gene Regulation
Transcription factor
Neoplasm Staging
Binding Sites
Base Sequence
Cell growth
Carcinoma
Cancers and Neoplasms
DNA Methylation
Latent TGF-beta Binding Proteins
Cancer research
Gene expression
Transcription Factors
Transforming growth factor
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 8
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....cbc7fa55a064e12d7640f29c98786845