Loss of human β-defensin 1, 2, and 3 expression in oral squamous cell carcinoma

S. Joly, L. M. Compton, C. Pujol, Z. B. Kurago, J. M. Guthmiller

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Introduction: Human β-defensins (HBDs) are cationic, antimicrobial peptides produced by epithelial cells and involved in various aspects of the innate and acquired immune responses. They are expressed by oral tissues as constitutive and inducible genes. Recently, single nucleotide polymorphisms (SNPs) of β-defensins have been correlated with increased susceptibility to certain diseases. Studies have reported altered expression of β-defensins in cancers suggesting their involvement in carcinogenesis. The purpose of this study was to evaluate the regulation of HBD-1 (also published as DEFB1), HBD-2 (DEFB4) and HBD-3 (DEFB103A) (http://www.genenames.org/index.html) and HBD-1 SNPs in oral squamous cell carcinoma cell lines (OSCC) and healthy gingival keratinocytes. Methods: β-defensin expression was quantitatively assessed using real-time polymerase chain reactions in OSCC and control cell lines after exposure to interleukin-1β, tumor necrosis factor-α, and interferon-γ. Control data were obtained in a previous study. DNA from 19 OSCC cell lines and 44 control subjects were extracted and the HBD-1 region spanning the 5′ untranslated region to the first intron was sequenced and analysed for SNP identification and distribution. Results: HBD-1 and HBD-2 basal messenger RNA expression were significantly lower in OSCC. In addition, the ability to be induced was significantly reduced in OSCC for all three β-defensins. Four HBD-1 SNPs were differentially distributed between cancer and control populations. Genotype distribution at the HBD-1 locus also suggested loss of heterozygosity in OSCC. Conclusions: The genetic variation observed in OSCC compared with that in control cell lines may account for differences in β-defensin expression. These results suggest a putative role for β-defensins in carcinogenesis and indicate that β-defensins may be useful markers of OSCC.

Original languageEnglish (US)
Pages (from-to)353-360
Number of pages8
JournalOral Microbiology and Immunology
Volume24
Issue number5
DOIs
StatePublished - Oct 1 2009
Externally publishedYes

Keywords

  • Linkage disequilibrium
  • Loss of heterozygosity
  • Oral cancer
  • Single nucleotide polymorphisms
  • β-defensins

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Dentistry(all)
  • Microbiology (medical)

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