Redox regulation of matrix metalloproteinase gene family in small cell lung cancer cells

Niramol Savaraj, Yingjie Wei, Hitoshi Unate, Pei Man Liu, C. J. Wu, Medhi Wangpaichitr, Diran Xia, Hong Ji Xu, Shi Xu Hu, M. Tien Kuo

Research output: Contribution to journalArticle

21 Citations (Scopus)

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 γ-glutamylcysteine synthetase (γ-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 γ-GCSh-transfected cells and their nontransfected counterpart. We observed downregulation of several matrix metalloproteinases (MMPs), i.e., MMP1 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 γ-GCSh expression using tetracycline-inducible γ-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.

Original languageEnglish
Pages (from-to)373-381
Number of pages9
JournalFree Radical Research
Volume39
Issue number4
DOIs
StatePublished - Apr 1 2005

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Small Cell Lung Carcinoma
Matrix Metalloproteinases
Oxidation-Reduction
Genes
Cells
Metalloproteins
Down-Regulation
Tumors
Glutamate-Cysteine Ligase
Biosynthesis
Microarray Analysis
Microarrays
Tetracycline
Oligonucleotide Array Sequence Analysis
Northern Blotting
Glutathione
Reactive Oxygen Species
Neoplasms
Complementary DNA
Antioxidants

Keywords

  • γ-glutamylcysteine synthetase
  • Matrix metalloproteins
  • ROS
  • Tumor invasion

ASJC Scopus subject areas

  • Biochemistry

Cite this

Redox regulation of matrix metalloproteinase gene family in small cell lung cancer cells. / Savaraj, Niramol; Wei, Yingjie; Unate, Hitoshi; Liu, Pei Man; Wu, C. J.; Wangpaichitr, Medhi; Xia, Diran; Xu, Hong Ji; Hu, Shi Xu; Kuo, M. Tien.

In: Free Radical Research, Vol. 39, No. 4, 01.04.2005, p. 373-381.

Research output: Contribution to journalArticle

Savaraj, Niramol ; Wei, Yingjie ; Unate, Hitoshi ; Liu, Pei Man ; Wu, C. J. ; Wangpaichitr, Medhi ; Xia, Diran ; Xu, Hong Ji ; Hu, Shi Xu ; Kuo, M. Tien. / Redox regulation of matrix metalloproteinase gene family in small cell lung cancer cells. In: Free Radical Research. 2005 ; Vol. 39, No. 4. pp. 373-381.
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