Article

ALPK2 is crucial for luminal apoptosis and DNA repair-related gene expression in a three-dimensional colonic-crypt model.

Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
Anticancer research (impact factor: 1.73). 06/2012; 32(6):2301-8. pp.2301-8
Source: PubMed

ABSTRACT Oncogenic KRAS signaling is dysregulated in a three-dimensional (3D)-specific manner in human colorectal cancer (CRC) HCT116 cells. However, the identity of the crucial genes which are down-regulated through oncogenic KRAS in 3D cultures remains unclear.
We established a specific anti-alpha-kinase 2 (ALPK2) antibody and addressed the ALPK2 function in HKe3 cells, which are HCT116 cells with a disruption in oncogenic KRAS, in a 3D colonic-crypt model.
In HKe3 cells grown in 3D culture, ALPK2 siRNA inhibited luminal apoptosis and reduced the expression of cleaved caspase-3. Furthermore, ALPK2 siRNA reduced the expression of DNA repair genes. Reduced expression of ALPK2 mRNA was found to be correlated with clinical colorectal adenomas in a public dataset of gene expression analyses.
ALPK2, down-regulated by oncogenic KRAS, is crucial for luminal apoptosis and expression of DNA repair-related genes, possibly in the transition of normal colonic crypt to adenoma.

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Keywords

3D)-specific manner
 
adenoma
 
ALPK2
 
ALPK2 function
 
ALPK2 mRNA
 
ALPK2 siRNA
 
ALPK2 siRNA inhibited luminal apoptosis
 
cleaved caspase-3
 
clinical colorectal adenomas
 
crucial genes
 
disruption
 
DNA repair-related genes
 
gene expression analyses
 
genes
 
luminal apoptosis
 
oncogenic KRAS
 
Oncogenic KRAS signaling
 
public dataset
 
Reduced expression
 
three-dimensional