Inhibition of nfκb reduces cellular viability in gh3 pituitary adenoma cells

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Objective: Adenomas of the pituitary gland are among the most common types of tumors of the adult brain. Although adenomas are histologically benign, they may be associated with significant morbidity and mortality, mostly because of their invasive growth pattern and hormone hypersecretion. Current medical therapies are suppressive, acting at a receptor level. Thus, there is a need to identify novel cellular and molecular targets for pituitary tumors. We investigated the possible role of the NFκB transcription factor in pituitary tumor cell growth. METHODS: The effect of NFκB pathway inhibition on cellular viability was studied in the GH3 pituitary adenoma cell line, a well-characterized rat cell line that secretes growth hormone and prolactin. Cells were treated with mechanistically diverse pharmacological NFκB pathway inhibitors or with molecular inhibitors that were overexpressed in tumor cells before the assessment of cellular viability. NFκB activity was also assessed in GH3 cells using deoxyribonucleic acid binding assays. RESULTS: GH3 cells exhibited constitutive NFκB activity, which contributed to increased cellular proliferation. Treatment with wedelolactone, an IκB kinase inhibitor, or overexpression of an IκB super-repressor reduced cell viability, further implicating NFκB in pituitary tumor cell growth. Pharmacological or molecular inhibition of Akt similarly reduced GH3 viability and NFκB binding, suggesting that constitutive activation of NFκB may be, at least in part, mediated by Akt. CONCLUSION: Directed targeting of the Akt and NFκB signaling pathways may be a useful adjunct in the clinical management of pituitary tumors. Further elucidation of this pathway may yield novel information regarding the behavior of pituitary tumors in humans.

Original languageEnglish (US)
Pages (from-to)1122-1127
Number of pages6
JournalNeurosurgery
Volume62
Issue number5
DOIs
StatePublished - May 1 2008

Keywords

  • Adenoma
  • Akt
  • IκB
  • IκB kinase
  • NFκB
  • Pituitary
  • Proliferation

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

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