PUBLICATION
Epigenetic silencing of NKD2, a major component of Wnt signaling, promotes breast cancer growth
- Authors
- Dong, Y., Cao, B., Zhang, M., Han, W., Herman, J.G., Fuks, F., Zhao, Y., Guo, M.
- ID
- ZDB-PUB-150701-5
- Date
- 2015
- Source
- Oncotarget 6(26): 22126-38 (Journal)
- Registered Authors
- Zhao, Yali
- Keywords
- DNA methylation, NKD2, Wnt signaling, breast cancer, epigenetics
- MeSH Terms
-
- Animals
- Breast Neoplasms/genetics*
- Breast Neoplasms/pathology
- Carrier Proteins/genetics*
- Cell Growth Processes/genetics
- Cell Line, Tumor
- DNA Methylation
- Female
- Gene Silencing
- Heterografts
- Humans
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Promoter Regions, Genetic
- Wnt Signaling Pathway/genetics*
- PubMed
- 26124080 Full text @ Oncotarget
Citation
Dong, Y., Cao, B., Zhang, M., Han, W., Herman, J.G., Fuks, F., Zhao, Y., Guo, M. (2015) Epigenetic silencing of NKD2, a major component of Wnt signaling, promotes breast cancer growth. Oncotarget. 6(26):22126-38.
Abstract
Naked cuticle homolog 2 (NKD2) has been reported to antagonize Wnt signaling in zebrafish, mouse and mammals. The aim of this study is to investigate the epigenetic changes and mechanisms of NKD2 in human breast cancer development. Six breast cancer cell lines (MCF-7, ZR75-1, MDA-MB-468, MDA-MB-231, T47D and BT474) and 68 cases of primary human breast cancer were studied using methylation specific PCR, immunohistochemistry, western blot, flow cytometry techniques and a xenograft mouse model. The expression of NKD1 and NKD2 was regulated by promoter region methylation in breast cancer cells. No NKD1 methylation was found in primary human breast cancer. NKD2 was methylated in 51.4% (35/68) of human primary breast cancer samples. NKD2 methylation was significantly associated with reduction of NKD2 expression, and tumor stage (p < 0.05). NKD2 suppressed breast cancer cell proliferation both in vitro and in vivo. NKD2 induced G1/S arrest and inhibited Wnt signaling in breast cancer cells. In conclusion, NKD2 is frequently methylated in human breast cancer, and the expression of NKD2 is regulated by promoter region methylation. NKD2 suppresses breast cancer proliferation by inhibiting Wnt signaling.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping