Regulation of IAPs gene family by interleukin-1 alpha and Epstein-Barr virus in nasopharyngeal carcinoma

Head Neck. 2008 Dec;30(12):1575-85. doi: 10.1002/hed.20896.

Abstract

Background: Inhibitors of apoptosis proteins (IAPs), which counteract apoptosis by potently inhibiting caspase activation, are promising targets of new anti-tumor therapy. However, their roles in the pathogenesis of nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-associated carcinoma, are not fully understood. Herein, we investigated the expression and regulation of IAPs in NPC.

Methods and results: Using real-time quantitative polymerase chain reaction (PCR) analysis, we found that among the IAPs family only the transcription of survivin, HIAP-1, and HIAP-2 was consistently up-regulated in NPC and metastatic NPC tissues. Immunohistochemical staining showed that their proteins were more predominantly expressed in tumor cells nests. Noteworthy, these IAPs were upregulated by interleukin-1 alpha stimulation or EBV infection, and subsequently resulted in triggering rapid proliferation of NPC verified by strong Ki-67 staining.

Conclusion: Survivin, HIAP-1, and HIAP-2 were distinctly upregulated in NPC, suggesting they may play significant roles in NPC tumorigenesis and serve as tumor markers with prognostic and therapeutic implications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / virology
  • Caspases / metabolism
  • Epstein-Barr Virus Infections / genetics*
  • Epstein-Barr Virus Infections / virology
  • Herpesvirus 4, Human / genetics*
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics*
  • Interleukin-1alpha / genetics
  • Microtubule-Associated Proteins / genetics*
  • Nasopharyngeal Neoplasms / genetics*
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / virology
  • Polymerase Chain Reaction
  • Survivin

Substances

  • BIRC5 protein, human
  • Biomarkers, Tumor
  • Inhibitor of Apoptosis Proteins
  • Interleukin-1alpha
  • Microtubule-Associated Proteins
  • Survivin
  • Caspases