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The human kallikrein 10 promoter contains a functional retinoid response element

  • Musheng Zeng , Ying Zhang , Ishfaq Bhat , David E. Wazer , Hamid Band and Vimla Band
Published/Copyright: June 26, 2006
Biological Chemistry
From the journal Volume 387 Issue 6

Abstract

Human kallikrein 10 (hK10) protein is expressed in normal breast but is significantly downregulated in a majority of invasive breast cancers. Thus, understanding how hK10 expression is regulated is of substantial significance. In this study, we analyzed the promoter region of hK10 using a website software (TRANSFAC 3.0), which predicted three possible retinoic acid response elements (RAREs), RARE1 at -1041 (TGACCTCGTGATCC), RARE2 at -859 (TGACCTCCTATGA) and RARE3 at -765 (TGACCTCCTGTGA), each with a half-site of a canonical sequence (TGACCT; reverse complement AGGTCA). Using electrophoretic mobility shift assays and nucleotide competition analysis, as well as chromatin immunoprecipitation of the native hK10 promoter, we demonstrated specific binding of RXR only to RARE1. The functional importance of RARE in the hK10 promoter was demonstrated by retinoid induction of hk10 promoter-reporters; furthermore, mutation of RARE1 but not of RARE2 or RARE3 abolished the induction of the reporter. Finally, we demonstrated the induction of hK10 mRNA and protein expression upon retinoid treatment of cells. In view of the correlation of the downregulation of hK10 mRNA and protein with breast cancer progression, these findings suggest a potential approach to restore hK10 expression in cancer patients.

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Published Online: 2006-06-26
Published in Print: 2006-06-01

©2006 by Walter de Gruyter Berlin New York

Articles in the same Issue

  1. The First International Symposium on Kallikreins
  2. A comprehensive nomenclature for serine proteases with homology to tissue kallikreins
  3. The kallikrein world: an update on the human tissue kallikreins
  4. Cellular distribution of human tissue kallikreins: immunohistochemical localization
  5. The tissue kallikrein-kinin system protects against cardiovascular and renal diseases and ischemic stroke independently of blood pressure reduction
  6. Proteinase-mediated cell signalling: targeting proteinase-activated receptors (PARs) by kallikreins and more
  7. Recombinant kallikrein expression: site-specific integration for hK6 production in human cells
  8. Kallikrein-related peptidase (KLK) family mRNA variants and protein isoforms in hormone-related cancers: do they have a function?
  9. The role of kallikrein-related peptidases in prostate cancer: potential involvement in an epithelial to mesenchymal transition
  10. Human kallikrein 10, a predictive marker for breast cancer
  11. Activation and enzymatic characterization of recombinant human kallikrein 8
  12. Human tissue kallikrein 9: production of recombinant proteins and specific antibodies
  13. The human kallikrein 10 promoter contains a functional retinoid response element
  14. Human kallikrein 4: enzymatic activity, inhibition, and degradation of extracellular matrix proteins
  15. Kallikrein-related peptidase 14 may be a major contributor to trypsin-like proteolytic activity in human stratum corneum
  16. A sensitive proximity ligation assay for active PSA
  17. Multiple mechanisms underlie the aberrant expression of the human kallikrein 6 gene in breast cancer
  18. Expression of the human kallikrein genes 10 (KLK10) and 11 (KLK11) in cancerous and non-cancerous lung tissues
  19. mRNA expression analysis of human kallikrein 11 (KLK11) may be useful in the discrimination of benign prostatic hyperplasia from prostate cancer after needle prostate biopsy
  20. The epigenetic basis for the aberrant expression of kallikreins in human cancers
  21. Improved prostate cancer detection with a human kallikrein 11 and percentage free PSA-based artificial neural network
  22. Overexpression of the human tissue kallikrein genes KLK4, 5, 6, and 7 increases the malignant phenotype of ovarian cancer cells
  23. Inhibition profiles of human tissue kallikreins by serine protease inhibitors
  24. Kallikrein-mediated cell signalling: targeting proteinase-activated receptors (PARs)
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