The effect of adenovirus-conjugated NDRG2 on p53-mediated apoptosis of hepatocarcinoma cells through attenuation of nucleotide excision repair capacity.

Abstract	NDRG2 mRNA and protein levels can be upregulated in a p53-dependent manner. NDRG2 enhances p53-mediated apoptosis, whereas overexpression of NDRG2 suppresses tumor cell growth, regardless of whether p53 is mutated. However, the complicated mechanism by which NDRG2 suppresses tumor cell growth and enhances apoptosis mediated by p53 is not fully understood. Here, we demonstrated that Ad-NDRG2 enhanced the apoptosis of HepG2 cells (wild-type p53). Additionally, Ad-NDRG2 combined with rAd-p53 enhanced the apoptosis of Huh7 cells (mutant p53) after chemotherapy, and the expression of the ERCC6 gene (Cockayne syndrome group B protein gene) was suppressed in this process. Ad-NDRG2 combined with rAd-p53 induced the apoptosis of tumor cells (HepG2 and Huh7 cells); however, apoptosis was attenuated after transfection with ERCC6. Our results indicate that Ad-NDRG2 enhances the p53-mediated apoptosis of hepatocarcinoma cells (HepG2 and Huh7) by attenuating the nucleotide excision repair capacity (i.e., by downregulating ERCC6), and ERCC6 is a NDRG2-inducible target gene that is involved in the p53-mediated apoptosis pathway.
Authors	Wei Cao, Ju-liang Zhang, Da-yun Feng, Xue-wu Liu, Yan Li, Li-feng Wang, Li-bo Yao, Hongxin Zhang, Jian Zhang
Journal	Biomaterials (Biomaterials) Vol. 35 Issue 3 Pg. 993-1003 (Jan 2014) ISSN: 1878-5905 [Electronic] Netherlands
PMID	24383128 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	NDRG2 protein, human Poly-ADP-Ribose Binding Proteins Tumor Suppressor Protein p53 Tumor Suppressor Proteins DNA Helicases ERCC6 protein, human DNA Repair Enzymes
Topics	Adenoviridae (genetics) Animals Apoptosis Carcinoma, Hepatocellular (genetics, pathology) Cell Line, Tumor DNA Helicases (genetics) DNA Repair DNA Repair Enzymes (genetics) Gene Expression Regulation, Neoplastic Hep G2 Cells Humans Liver (metabolism, pathology) Liver Neoplasms (genetics, pathology) Mice Mice, Nude Poly-ADP-Ribose Binding Proteins Transfection Tumor Suppressor Protein p53 (genetics, metabolism) Tumor Suppressor Proteins (genetics) Up-Regulation

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