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C-jun inhibits mammary apoptosis in vivo.

By Sanjay Katiyar, Mathew C Casimiro, Luis Dettin, Xiaoming Ju, Erwin F Wagner, Hirokazu Tanaka and Richard Pestell

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

Topics: 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
Publisher: Jefferson Digital Commons
Year: 2010
OAI identifier: oai:jdc.jefferson.edu:cbfp-1044

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