Effects of JNK on TGF-beta responses of mouse B lymphoma derived A20 cells

TGF-beta plays multiple functions in a board range of cellular responses such as proliferation, differentiation, motility and survival by activating several cellular signaling pathways, including Smads and MAP kinases (Erk, JNK and p38). In particular, TGF-beta can activate pro- or anti-apoptotic signals depending on the target cells. We found that blockage of JNK activation sensitized mouse B lymphoma derived A20 cells to TGF-beta-induced apoptosis. These results suggest that TGF-beta activate JNK to inhibit the activation of death signal that is simultaneously activated by TGF-beta. We used microarrays to gain insight into the effects of JNK inhibition on gene expression in TGF-b-stimulated A20 cells and identified JNK-dependent TGF-beta inducible genes. Keywords: time course The following six samples were prepared: untreated A20 cells (non-stimulated, DMSO): A20 cells cultured with SP600125 for 24 h (non-stimulated, SP600125): A20 cells stimulated with TGF-beta for 12 h (TGF-beta 12 h, DMSO) and 24 h (TGF-beta 24 h, DMSO): and A20 cells stimulated with TGF-beta in the presence of SP600125 for 12 h (TGF-beta 12 h, SP600125) and 24 h (TGF-beta 24 h, SP600125), respectively. Total RNA was prepared and hybridized to the Affymetrix Mouse Genome 430 2.0 array. Genes whose expression was increased by more than 2-fold at either 12 or 24 h after TGF-beta stimulation were identified as TGF-beta inducible genes. Amongst them, we identified genes whose induction levels were reduced by more than 75% by co-treatment with the JNK inhibitor SP600125.