Promoter methylation, mutation, and genomic deletion are involved in the decreased NDRG2 expression levels in several cancer cell lines.
Human NDRG2 (N-Myc downstream regulated gene 2) was identified as a candidate tumor suppressor gene due to its low expression in human glioma and other cancer tissues. However, the mechanisms that lead to inactivation of the NDRG2 gene remain unknown. In the present study, semi-quantitative RT-PCR and Western blot analysis were used to confirm that NDRG2 mRNA and protein levels are decreased in several cancer cell lines. We found heterozygous deletion of NDRG2 in MCF-7 cells, and showed that mutation (at -13bp (C>T)) and methylation of the NDRG2 promoter occurred in several cancer cell lines. Furthermore, mutation (-13bp (C>T)) of the NDRG2 core promoter significantly reduced NDRG2 activity. Finally, we showed that NDRG2 expression was decreased in several breast cancer tissues. Unexpectedly, changes in the NDRG2 gene were not observed. Here, we describe for the first time, the mechanisms involved in NDRG2 gene down-regulation.
Liu
Na
N
Department of Biochemistry and Molecular Biology, The Center of Molecular Medicine, The Fourth Military Medical University, The State Key Laboratory of Cancer Biology, 17 Changle Western Road, 710032 Xi'an, People's Republic of China.
Wang
Lifeng
L
Liu
Xinping
X
Yang
Qi
Q
Zhang
Jing
J
Zhang
Wei
W
Wu
Yousheng
Y
Shen
Lan
L
Zhang
Yingqi
Y
Yang
Angang
A
Han
Hua
H
Zhang
Jian
J
Yao
Libo
L
D001483:Base Sequence; D045744:Cell Line, Tumor; D019175:DNA Methylation; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
C466228:NDRG2 protein, human; D025521:Tumor Suppressor Proteins