Expression of the constitutively activated RelA/NF-κB in human astrocytic tumors and the in vitro implication in the regulation of urokinase-type plasminogen activator, migration, and invasion

Keishi Tsunoda, Gaspar Kitange, Takeo Anda, Hamisi Kimaro Shabani, Makio Kaminogo, Shobu Shibata, Izumi Nagata

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Although malignant gliomas are highly invasive tumors, a characteristic that contributes to the commonly observed therapeutic failures and local disease recurrences, the molecular events that regulate invasion in these tumors remain poorly understood. Because the transcription factor RelA/NF-κB has been shown to regulate invasion during several cellular processes, we have examined immunohistochemically expression of the constitutively activated RelA/NF-κB in tissues obtained from 49 astrocytic tumors [8 diffuse astrocytomas, 9 anaplastic astrocytomas (AAs) and 32 glioblastomas (GBMs)]. In addition, we examined the in vitro effects of antisense oligonucleotides and curcumin on the expression and activation of RelA/NF-κB, urokinase-type plasminogen activator (u-PA) expression, migration, and invasion in the T98G glioma cell line. Expression of the constitutively activated RelA/NF-κB was observed in 2 (25%) of 8 cases of diffuse astrocytomas, 5 (55.6%) of 9 cases of AAs, and 30 (93.8%) of 32 cases of GBMs. This expression was significantly correlated with the malignant potential in astrocytic tumors (P < 0.001). Moreover, antisense oligonucleotides and curcumin inhibited phorbol-12- myristate-13-acetate (PMA)-induced RelA/NF-κB expression or activation (or both), down-regulated u-PA expression, and reduced the migration and invasive potentials of T98G glioma cells. Thus, the expression of constitutively activated RelA/NF-κB is associated with malignancy potential in astrocytic tumors and may play a critical role in the regulation of u-PA expression and invasiveness in gliomas. RelA/NF-κB may therefore be an intriguing candidate for studies aimed at understanding and prevention of the invasiveness of gliomas.

Original languageEnglish (US)
Pages (from-to)79-87
Number of pages9
JournalBrain Tumor Pathology
Volume22
Issue number2
DOIs
StatePublished - Dec 2005
Externally publishedYes

Keywords

  • Glioma
  • Invasion
  • Migration
  • NF-κB
  • u-PA

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