Inverse correlation between p16INK4A expression and NF-κB activation in melanoma progression

Paola Ghiorzo, Michela Mantelli, Sara Gargiulo, Claudia Gramigni, Lorenza Pastorino, Barbara Banelli, Barbara Villaggio, Maria Cristina Coccia, Angela Rita Sementa, Cecilia Garrè, Giovanna Bianchi-Scarrà

Research output: Contribution to journalArticlepeer-review

Abstract

Expression of p16INK4A, the product of the melanoma susceptibility gene CDKN2A, has been shown to decrease in correlation with tumor progression. P16INK4A is a key regulator of cell-cycle function, and likely interacts with a variety of targets alongside cyclin-dependent kinases (CDKs). One such target is nuclear factor KB (NF-κB), a pleiotropic transcription factor that plays a crucial role in apoptosis, oncogenesis and cell cycle control. NF-κB p65 has been shown to be activated in melanoma cell lines but few studies decribe its expression in the tissue. In the present study we focused on synchronous expression of p16INK4A and NF-κB p65 and their functional activation in melanoma cell lines and biopsy tissue. Activation of NF-κB p65, as observed by electrophoretic mobility shift assay in cell lines, was correlated with expression and cellular localization of the active and inactive forms of its inhibitor, IκB-α. In melanocytic lesions, p16INK4A and NF-κB p65 expression were inversely correlated with levels of the nuclear component of NF-κB p65 increasing from nevi to primary melanomas and metastases.

Original languageEnglish
Pages (from-to)1029-1037
Number of pages9
JournalHuman Pathology
Volume35
Issue number8
DOIs
Publication statusPublished - Aug 2004

Keywords

  • CDK
  • CDKN2A/p16INK4A
  • cyclin-dependent kinase
  • electrophoretic mobility shift assay
  • EMSA
  • expression
  • immunohistochemistry
  • LOH
  • loss of heterozygosity
  • melanoma progression
  • NF
  • NF-κB p65
  • NHEM
  • normal human epithelial melanocytes
  • nuclear factor
  • TNF

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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