research
C-jun inhibits mammary apoptosis in vivo.
Abstract
c-jun, which is overexpressed in a number of human cancers encodes a critical component of the AP-1 complex. c-jun has been shown to either induce or inhibit cellular apoptosis. Germ line deletion of both c-jun alleles is embryonically lethal. To determine the role of the endogenous c-jun gene in apoptosis, we performed mammary epithelial cell-targeted somatic deletion using floxed c-jun (c-jun(f/f)) conditional knockout mice. Laser capture microdissection demonstrated endogenous c-jun inhibits expression of apoptosis inducing genes and reactive oxygen species (ROS)-reducing genes (MnSOD, catalase). ROS have been implicated in apoptosis and undergo enzymatic elimination via MnSOD and CuZnSOD with further detoxification via catalase. c-jun-mediated survival was in part dependent on ROS production. c-jun-mediated repression of MnSOD and catalase occurred via mitochondrial complex I and NOX I. Collectively, these studies define a pivotal role of endogenous c-jun in promoting cell survival via maintaining mitochondrial integrity and expression of the key regulators of ROS production- article
- Animals
- Apoptosis
- Catalase
- Cell Survival
- Electron Transport Complex I
- Enzyme-Linked Immunosorbent Assay
- Female
- Fluorescent Antibody Technique
- Gene Expression Regulation
- Genes
- jun
- Glutathione Peroxidase
- Inhibitor of Apoptosis Proteins
- Mammary Glands
- Animal
- Membrane Potential
- Mitochondrial
- Mice
- Mice
- Knockout
- Mice
- Transgenic
- NADH
- NADPH Oxidoreductases
- Proto-Oncogene Proteins c-jun
- Reactive Oxygen Species
- Repressor Proteins
- Signal Transduction
- Superoxide Dismutase
- Transcription Factor AP-1
- Genes, jun
- Mammary Glands, Animal
- Membrane Potential, Mitochondrial
- Mice, Knockout
- Mice, Transgenic
- NADH, NADPH Oxidoreductases
- Oncology