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Methylation of Wnt7a is modulated by DNMT1 and cigarette smoke condensate in non-small cell lung cancer
- Source :
- PLoS ONE, Vol 7, Iss 3, p e32921 (2012), PLoS ONE
- Publication Year :
- 2012
- Publisher :
- Public Library of Science (PLoS), 2012.
-
Abstract
- Wnt7a is known to be a tumor suppressor that is lost in NSCLC, but no mechanism of loss has been established. Methylation of promoter regions has been established as a common mechanism of loss of tumor suppressor expression in NSCLC. We previously demonstrated that loss of Wnt7a in non-transformed lung epithelial cell lines led to increased cell growth, altered 3-D culture growth, and increased migration. The Wnt7a promoter has a higher percentage of methylation in NSCLC tumor tissue compared to matched normal lung tissue and methylation of the promoter region leads to decreased activity. We treated H157 and H1299 NSCLC cell lines with 5-Aza-2′-deoxycytidine and detected loss of Wnt7a promoter methylation, increased Wnt7a expression, and increased activity of the Wnt7a lung signaling pathway. When DNMT1 expression was knocked down by shRNA, expression of Wnt7a increased and methylation decreased. Together these data suggest that in NSCLC, Wnt7a is lost by methylation in a subset of tumors and that this methylation is maintained by DNMT1. Restoration of Wnt7a expression through demethylation could be an important therapeutic approach in the treatment of NSCLC.
- Subjects :
- Pathology
Lung Neoplasms
Pulmonology
Cancer Treatment
lcsh:Medicine
Biochemistry
Lung and Intrathoracic Tumors
Small hairpin RNA
0302 clinical medicine
Carcinoma, Non-Small-Cell Lung
Smoke
Nucleic Acids
Molecular Cell Biology
DNA (Cytosine-5-)-Methyltransferases
Promoter Regions, Genetic
lcsh:Science
Lung
0303 health sciences
Multidisciplinary
Smoking
Methylation
3. Good health
Phenotype
Oncology
030220 oncology & carcinogenesis
DNA methylation
Azacitidine
Medicine
Signal transduction
Research Article
DNA (Cytosine-5-)-Methyltransferase 1
medicine.medical_specialty
Biology
Decitabine
03 medical and health sciences
medicine
Genetics
Lung cancer
030304 developmental biology
Cell growth
lcsh:R
Cancers and Neoplasms
Promoter
Epithelial Cells
DNA
DNA Methylation
medicine.disease
respiratory tract diseases
Wnt Proteins
Cancer research
DNMT1
lcsh:Q
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 7
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....3b6fa44f5bb2c8e1645584f4ab4d94b8