Differential expression of NFkB and response to oxidative stress in normal human melanocytes and metastatic melanoma cells

Abstract

ESDR / JSID / SID Abstracts 0590 DIFFERENTIAL EXPRESSION OF NFKB AND RESPONSE TO OXIDATIVE STRESS IN NORMAL HUMAN MEIANOCYTES AND METASTATIC MELANOMA CELLS. - .. ...:n~.. 4.» . .2 . 3., .u.:..:. :n.- A .- n,__1;qmg]gu, Univeulty or Callomla-irvlne, Chen Family comprehensive Cancer Center. Orange. CA The transcription factor NFRB is activated by a variety of stimuli including inflammatory cytokinee and reactive oxygen Snecies (H08). The dlmericoornplexesolNFk8belongtothe Fteltemiy. Twooitheee complexes, p50 (NFRBI) and p75 (c»Rel). ere invereely expreeeed in fl0l'I1|I| humen melenocytee (NHM) end meteletic melanoma (MM) as determined by Notthem analysis. We beset DNA binding activity ot NFltB inlhllwesstoldthet in NHM. NFKB isconetitutively active in LIA probably as a consequence of the transformed phenotype. Cells were treated with iree (F) or enzymrgenereted (GO. gluooeelgiucoee oxideee) hydrogen peroxide. Bieuttoscernine (B80) was ueed to inhbit the production of giutethione (GSH). an endogenous antioxidant. The expreeeion oi p50 in MMdecreuedw‘l6ertd709lIlol|owinqGOartdF.reqgeotlvetyend decreased 89% following 380 treatment. DNA binding activity at NFlta in MM increased 5 fold after F or 00 treatment and 20 fold after 380 treatment. NHM were not attested by any treatment. GSH, being uneveidale to the cell loliowing BSO treatment. led to lncreeeed endogenous nos lu-ther Increeeing Ni-‘k8 ectivily in Mt. The dvterentiel reeponsesofNFkBinNI-iMandMMmeyse~eeseueetultergeitov preventive and therapeutic interventions. S99