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Urological Research

, Volume 25, Issue 4, pp 231–238 | Cite as

Molecular regulation of intercellular adhesion molecule 1 (ICAM-1) expression in renal cell carcinoma

  • K. Tanabe
  • S. C. Campbell
  • J. P. Alexander
  • F. Steinbach
  • M. G. Edinger
  • R. R. Tubbs
  • A. C. Novick
  • E. A. Klein
Original Paper

Abstract

Intercellular adhesion molecule-1 (ICAM-1) mediates two important functional. aspects of tumor biology, namely enhancement of tumor metastasis and mediation of host defense mechanisms such as lymphocyte-mediated tumor cytotoxicity. Since ICAM-1 is expressed by most renal cell carcinomas (RCC), the regulation of ICAM-1 expression is important in understanding the biological behavior of RCC. We report an investigation on ICAM-1 expression and molecular regulation by cytokines and protein kinase C activator on RCC cell lines. Of the various cytokines, tumor necrosis factor αa (TNFα), interferon-γ (IFNγ), and phorbol myristate acetate (PMA) strongly upregulated ICAM-1 protein expression on RCC. The kinetics of ICAM-1 message induction was studied by Northern analysis of total RNA extracted from RCC and normal kidney proximal tubular (NKPT) cells. Time course studies showed that ICAM-1 mRNA was upregulated by INFγ, TNFα, and PMA, plateaued after 2 h, and remained increased for up to 24 h. Although ICAM-1 mRNA in NKPT cells was upregulated by these cytokines, their messages returned to basal levels after 24 h. ICAM-1 mRNA stability assays showed that both unstimulated and stimulated RCC cells had very stable ICAM-1 mRNA up to 24 h. In order to investigate whether increased gene transcription contributes to ICAM-1 upregulation, RCC cells were treated with TNFα, IFNγ, or PMA with or without simultaneous addition of actinomycin D. ICAM-1 message induction-blocking studies suggested that primary upregulation of ICAM-1 mRNA may be caused by transcriptional upregulation. These results suggest that long-lasting ICAM-1 message upregulation in response to cytokines or PMA may be due to transcriptional upregulation in the early phase and stabilization of ICAM-1 message in the later phase (after 4 h). These observations suggest that RCC may lack the normal downregulatory mechanisms which control ICAM-1 expression and may explain the high frequency of ICAM-1 expression observed on primary human RCC.

Key words

ICAM-1 Molecular regulation Renal cell carcinoma Cytokines Protein kinase C activator 

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Copyright information

© Springer-Verlag 1997

Authors and Affiliations

  • K. Tanabe
    • 1
  • S. C. Campbell
    • 2
  • J. P. Alexander
    • 2
  • F. Steinbach
    • 2
  • M. G. Edinger
  • R. R. Tubbs
    • 3
  • A. C. Novick
    • 2
  • E. A. Klein
    • 2
  1. 1.Department of Urology, Kidney CenterTokyo Women's Medical CollegeShinjuku-ku, TokyoJapan
  2. 2.Department of UrologyThe Cleveland Clinic FoundationClevelandUSA
  3. 3.Department of PathologyThe Cleveland Clinic FoundationClevelandUSA

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