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NDN is an imprinted tumor suppressor gene that is downregulated in ovarian cancers through genetic and epigenetic mechanisms
- Source :
- Oncotarget
- Publication Year :
- 2015
-
Abstract
- NDN is a maternally imprinted gene consistently expressed in normal ovarian epithelium, is dramatically downregulated in the majority of ovarian cancers. Little or no NDN expression could be detected in 73% of 351 epithelial ovarian cancers. NDN was also downregulated in 10 ovarian cancer cell lines with total loss in 6 of 10. Re-expression of NDN decreased Bcl-2 levels and induced apoptosis, which significantly inhibited ovarian cancer cell growth in cell culture and in xenografts. In addition, re-expression of NDN inhibited cell migration by decreasing actin stress fiber and focal adhesion complex formation through deactivation of Src, FAK and RhoA. Loss of NDN expression in ovarian cancers could be attributed to LOH in 28% of 18 informative cases and to hypermethylation of CpG sites 1 and 2 of NDN promoter in 23% and 30% of 43 ovarian cancers, respectively. Promoter hypermethylation was also found in 5 of 10 ovarian cancer cell lines. Treatment with the demethylating agent 5-aza-2'-deoxycytidine restored NDN expression in 4 of 7 cell lines with enhanced promoter methylation levels. These observations support the conclusion that NDN is an imprinted tumor suppressor gene which affects cancer cell motility, invasion and growth and that its loss of function in ovarian cancer can be caused by both genetic and epigenetic mechanisms.
- Subjects :
- 0301 basic medicine
endocrine system diseases
Loss of Heterozygosity
Apoptosis
Bioinformatics
Epithelium
growth inhibition
chemistry.chemical_compound
Mice
0302 clinical medicine
Cell Movement
Stress Fibers
Medicine
tumor suppressor gene
Promoter Regions, Genetic
Ovarian Neoplasms
Nuclear Proteins
3. Good health
Gene Expression Regulation, Neoplastic
Oncology
Proto-Oncogene Proteins c-bcl-2
030220 oncology & carcinogenesis
DNA methylation
Azacitidine
Female
imprinting
Research Paper
Tumor suppressor gene
Proto-Oncogene Proteins pp60(c-src)
Mice, Nude
Nerve Tissue Proteins
NDN
cell motility
Decitabine
Polymorphism, Single Nucleotide
03 medical and health sciences
Cell Line, Tumor
Animals
Humans
Epigenetics
Focal Adhesions
FAK
business.industry
Cell growth
Tumor Suppressor Proteins
Ovary
DNA Methylation
medicine.disease
Demethylating agent
030104 developmental biology
chemistry
Focal Adhesion Kinase 1
Cancer cell
Cancer research
CpG Islands
business
Ovarian cancer
Genomic imprinting
rhoA GTP-Binding Protein
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 7
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....51d49ba0ab94301c3bf1d38c4822ea9f