Molecular Oncology
Volume 4, Issue 4 , Pages 347-356, August 2010

Cox-2 gene expression in chemically induced skin papillomas cannot predict subsequent tumor fate

  • Tomo-o Ishikawa

      Affiliations

    • Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
    • ,
  • Naveen K. Jain

      Affiliations

    • Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
    • ,
  • Harvey R. Herschman

      Affiliations

    • Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
    • Department of Biological Chemistry, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
    • Molecular Biology Institute, UCLA, Los Angeles, CA, USA
    • Corresponding Author InformationCorresponding author at: 341 Boyer Hall, UCLA, 611 Charles E. Young Drive East, Los Angeles, CA 90095, USA. Tel.: +1 310 825 8735; fax: +1 310 825 1447.

Received 27 February 2010; received in revised form 9 June 2010; accepted 9 June 2010. published online 23 June 2010.

Abstract 

Elevated cyclooxygenase-2 (COX-2) expression is observed in a variety of premalignant neoplastic tissues, suggesting COX-2 expression might serve as a potential indicator of subsequent tumor development. However, it has not been possible to compare the relationship between Cox-2 gene expression in premalignant lesions and their subsequent fate, because conventional studies require tissue destruction for analysis of gene expression. To monitor COX-2 expression non-invasively during tumor development, we created a Cox-2 luciferase knock-in mouse, Cox-2luc, in which the firefly luciferase coding region replaces the Cox-2 coding region. Luciferase activity was non-invasively, quantitatively and repeatedly monitored in Cox-2luc/+ mice subjected to DMBA/TPA multistage skin tumor induction. Luciferase activity is significantly higher in all papillomas than in surrounding skin. However, the magnitude of Cox-2 promoter-driven luciferase activity in small papillomas cannot predict subsequent papilloma regression or growth. Elevated Cox-2 promoter-driven luciferase signal can be detected when papillomas first become visible, but not before this time.

Keywords: Cyclooxygenase, Luciferase, Knock-in mouse, Gene expression, Skin cancer, DMBA/TPA

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PII: S1574-7891(10)00050-5

doi:10.1016/j.molonc.2010.06.004

Molecular Oncology
Volume 4, Issue 4 , Pages 347-356, August 2010

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