title: Redox regulation of matrix metalloproteinase gene family in small cell lung cancer cells.
abstract: It has been implicated that reactive oxygen species (ROS) play important roles in modulating tumor progression. However, the mechanisms by which redox-regulated tumor progression are largely unknown. We previously demonstrated that reduced intracellular redox conditions could be achieved in stably transfected small cell lung cancer cells with gamma-glutamylcysteine synthetase (gamma-GCSh) cDNA which encodes a rate-limiting enzyme in the biosynthesis of glutathione (GSH), a major physiological redox regulator. In the present study, using DNA microarray analyses, we compared the expression profiles between the gamma-GCSh-transfected cells and their nontransfected counterpart. We observed downregulation of several matrix metalloproteinases (MMPs), i.e., MMPI and MMP3, and MMP10 in the transfected cells. Dot blot and Northern blot hybridizations confirmed that, among the 18 MMP gene family members and four tissue inhibitors of matrix metalloprotein family (TIMP) analyzed, the expression levels of these three MMPs were consistently reduced. Transiently increased gamma-GCSh expression using tetracycline-inducible gamma-GCSh adenoviral expression system also showed down-regulation of MMP3 and MMP10, but not MMP1. Our results demonstrated that redox regulation of MMP1, MMP3 and MMP10 expression depend upon different modes of redox manipulation. These results bear implication that antioxidant modulation of antitumor progression may be contributed at least in part by the downregulation of a subset of metrix metalloproteins.
authors: Hematology/Oncology Section, Department of Medicine, VA Medical Center, University of Miami School of Medicine, Miami, FL 33125, USA. nsavaraj@med.miami.edu
authors: Niramol
authors: N
authors: Savaraj
authors: Yingjie
authors: Y
authors: Wei
authors: Hitoshi
authors: H
authors: Unate
authors: Pei-Man
authors: PM
authors: Liu
authors: C J
authors: CJ
authors: Wu
authors: Medhi
authors: M
authors: Wangpaichitr
authors: Diran
authors: D
authors: Xia
authors: Hong-Ji
authors: HJ
authors: Xu
authors: Shi-Xu
authors: SX
authors: Hu
authors: M
authors: M
authors: Tien Kuo
mesh_terms: D015152:Blotting, Northern; D015153:Blotting, Western; D018288:Carcinoma, Small Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005721:Glutamate-Cysteine Ligase / Q000096:biosynthesis / Q000235:genetics; D005978:Glutathione / Q000096:biosynthesis; D006801:Humans; D015151:Immunoblotting; D008175:Lung Neoplasms / Q000235:genetics*; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000032:analysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione