| First Author | Yan M | Year | 2008 |
| Journal | Neoplasia | Volume | 10 |
| Issue | 2 | Pages | 160-7 |
| PubMed ID | 18283338 | Mgi Jnum | J:136014 |
| Mgi Id | MGI:3794939 | Doi | 10.1593/neo.07935 |
| Citation | Yan M, et al. (2008) Endoplasmic reticulum stress and unfolded protein response in Atm-deficient thymocytes and thymic lymphoma cells are attributable to oxidative stress. Neoplasia 10(2):160-7 |
| abstractText | Both oxidative stress and endoplasmic reticulum (ER) stress have been implicated in carcinogenesis. It is well documented that cells deficient in the ataxia-telangiectasia mutated (ATM) gene undergo oxidative stress, which is critically involved in thymic lymphomagenesis in Atm-/- mice. Here we demonstrate that undifferentiated Atm-/- thymocytes show signs of ER stress and of the unfolded protein response (UPR). Using two-dimensional (2-D) gel electrophoresis and mass spectrometry (MS) analysis, we identified 22 differentially expressed proteins, including the ER stress marker glucose-regulated protein 78 (GRP78), in Atm-/- thymocytes and in Atm-/- thymic lymphoma cells relative to Atm+/+ thymocytes. The phosphorylated alpha subunit of eukaryotic translation initiation factor 2 (p-eIF2alpha), a UPR marker, was also increased in Atm-/- thymocytes. Cells of the ATL-1 line, which were derived from an Atm-/- mouse thymic lymphoma, were more sensitive to the ER stress inducer tunicamycin than were Atm+/+ thymic leukemia ASL-1 cells. Notably, treatment with hydrogen peroxide duplicated the effects of ATM deficiency in cultured thymocytes, and treatment with the novel cell-permeable thiol antioxidant N-acetylcysteine amide (AD4) reduced elevated p-eIF2alpha levels in thymocytes of Atm-/- mice. Thus, we propose that ER stress and the UPR are secondary to oxidative stress in Atm-/- thymocytes. |
