Tristetrapolin Binds to the COX-2 mRNA 3’ Untranslated Region in Cancer Cells

  • Olivier Boutaud
  • Dan A. Dixon
  • John A. Oates
  • Hitoshi Sawaoka
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 525)

Abstract

Consistent evidence of several types indicates that the inducible cyclooxygenase (COX-2) can promote the multi-step sequence of events that lead to colon cancer [1,2]. Levels of COX-2 are increased in 85-90% of human colorectal adencarcinoma [3]. It also is expressed in cancers of the stomach [4], esophagus [5], pancreas [6], prostate [7], lung [8], and breast [9]. Whereas it is clear that COX-2 plays an important role in the initiation of colon cancer, the mechanisms that lead to its over-expression have not been fully elucidated. COX-2 expression is regulated at the transcriptional level in response to cytokines [10] and oncogenic signaling pathways [11]. Also, post-transcriptional mechanisms have been shown to play a role in the regulation of COX-2 expression during carcinogenesis [12], and to increase [13] or decrease [14] COX-2 mRNA stability. The 3’ UTR of COX-2 mRNA contains 22 copies of a conserved AU-rich sequence element (ARE), the AUUUA pentamer. This pentamer, frequently located in or near a U rich region, has been associated with the regulation of the stability of a number of mRNAs, including those of proto-oncogenes and cytokines. A number of ARE-binding proteins have been identified, including HuR, AUF- 1/hnRNPD, TIA-1, and tristetraprolin, that can exert either positive or negative effects on stability, translation and subcellular localization of the mRNA [15, 16, 17].

Keywords

Zinc Adenocarcinoma Adenoma Dexamethasone Prostaglandin 

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Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Olivier Boutaud
    • 1
  • Dan A. Dixon
    • 2
  • John A. Oates
    • 3
  • Hitoshi Sawaoka
    • 4
  1. 1.Division of Clinical PharmacologyVanderbilt UniversityNashvilleUSA
  2. 2.School of Medicine, Department of SurgeryVanderbilt UniversityNashvilleUSA
  3. 3.Division of Clinical PharmacologyVanderbilt University School of Medicine, The Vanderbilt-Ingram Cancer CenterNashvilleUSA
  4. 4.School of Medicine, Department of PharmacologyVanderbilt UniversityNashvilleUSA

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