Molecular determinants for the cell death mode (CBX131). unidentified

We found that activation of ASC in COLO205 human colon adenocarcinoma cell line induces necrosis, while that in NUGC-4 human stomach cancer cell line induces apoptosis. CLC12N2 is a COLO205-derived stable cell line that expresses chimeric protein (C12N2) consisting of the CARD from CARD12 (NLRC4) and the NOD and LRRs from Nod2 (NLRC2), a sensor for muramyl dipeptide (MDP). MDP stimulation induces C12N2-mediated oligomerization of ASC and necrotic cell death in the original CLC12N2 cell line (clone 2). When we isolated subclones of CLC12N2, we found that MDP stimulation induced apoptosis in some subclones (such as clone 215 and 431), while the same stimulation induced necrosis in others (such as clone 144). In these experiments, we compared the expression levels of genes between CLC12N2 clones that exhibit necrosis and those exhibit apoptosis in response to MDP stimulation. We also compared the expression levels of genes between COLO205 and NUGC-4 cells.