title: The Breast Cancer Tumor Suppressor TRIM29 Is Expressed via ATM-dependent Signaling in Response to Hypoxia.
abstract: Reduced ATM function has been linked to breast cancer risk, and the TRIM29 protein is an emerging breast cancer tumor suppressor. Here we show that, in cultured breast tumor and non-tumorigenic mammary epithelial cells, TRIM29 is up-regulated in response to hypoxic stress but not DNA damage. Hypoxia-induced up-regulation of TRIM29 is dependent upon ATM and HIF1α and occurs through increased transcription of the TRIM29 gene. Basal expression of TRIM29 is also down-regulated in cells expressing diminished levels of ATM, and findings suggest that this occurs through basal NF-κB activity as knockdown of the NF-κB subunit RelA suppresses TRIM29 abundance. We have previously shown that the activity of the TWIST1 oncogene is antagonized by TRIM29 and now show that TRIM29 is necessary to block the up-regulation of TWIST1 that occurs in response to hypoxic stress. This study establishes TRIM29 as a hypoxia-induced tumor suppressor gene and provides a novel molecular mechanism for ATM-dependent breast cancer suppression.
authors.affiliation: From the Departments of Biochemistry and Molecular Biology and.
authors.forename: Muzaffer
authors.initials: M
authors.lastname: Dükel
authors.affiliation: Medicine, University of Florida College of Medicine, Gainesville, Florida 32610.
authors.forename: W Scott
authors.initials: WS
authors.lastname: Streitfeld
authors.affiliation: Medicine, University of Florida College of Medicine, Gainesville, Florida 32610.
authors.forename: Tsz Ching Chloe
authors.initials: TC
authors.lastname: Tang
authors.affiliation: From the Departments of Biochemistry and Molecular Biology and.
authors.forename: Lindsey R F
authors.initials: LR
authors.lastname: Backman
authors.affiliation: From the Departments of Biochemistry and Molecular Biology and.
authors.forename: Lingbao
authors.initials: L
authors.lastname: Ai
authors.affiliation: Medicine, University of Florida College of Medicine, Gainesville, Florida 32610.
authors.forename: W Stratford
authors.initials: WS
authors.lastname: May
authors.affiliation: From the Departments of Biochemistry and Molecular Biology and kdbrown1@ufl.edu.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Brown
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; C087296:TRIM29 protein, human; C103173:TWIST1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D051879:Twist-Related Protein 1; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: breast cancer; cell signaling; hypoxia; hypoxia-inducible factor (HIF); tumor suppressor gene