Fatigue and gene expression in human leukocytes: increased NF-κB and decreased glucocorticoid signaling in breast cancer survivors with persistent fatigue.

TitleFatigue and gene expression in human leukocytes: increased NF-κB and decreased glucocorticoid signaling in breast cancer survivors with persistent fatigue.
Publication TypeJournal Article
Year of Publication2011
AuthorsBower JE, Ganz PA, Irwin MR, Arevalo JMG, Cole SW
JournalBrain Behav Immun
Volume25
Issue1
Pagination147-50
Date Published2011 Jan
ISSN1090-2139
KeywordsBreast Neoplasms, Computational Biology, Diagnostic and Statistical Manual of Mental Disorders, Fatigue, Female, Gene Expression, Glucocorticoids, Humans, Hydrocortisone, Leukocytes, Middle Aged, NF-kappa B, Receptors, Glucocorticoid, RNA, Signal Transduction, Survivors
Abstract

Fatigue is highly prevalent in the general population and is one of the most common side effects of cancer treatment. There is growing evidence that pro-inflammatory cytokines play a role in cancer-related fatigue, although the molecular mechanisms for chronic inflammation and fatigue have not been determined. The current study utilized genome-wide expression microarrays to identify differences in gene expression and associated alterations in transcriptional activity in leukocytes from breast cancer survivors with persistent fatigue (n=11) and non-fatigued controls (n=10). We focused on transcription of inflammation-related genes, particularly those responsive to the pro-inflammatory NF-κB transcription control pathway. Further, given the role of glucocorticoids as key regulators of inflammatory processes, we examined transcription of glucocorticoid-responsive genes indicative of potential glucocorticoid receptor (GR) desensitization. Plasma levels of cortisol were also assessed. Consistent with hypotheses, results showed increased expression of transcripts with response elements for NF-κB, and reduced expression of transcripts with response elements for glucocorticoids (p<.05) in fatigued breast cancer survivors. No differences in plasma levels of cortisol were observed. These data indicate that increased activity of pro-inflammatory transcription factors may contribute to persistent cancer-related fatigue and provide insight into potential mechanisms for tonic increases in NF-κB activity, specifically decreased expression of GR anti-inflammatory transcription factors.

DOI10.1016/j.bbi.2010.09.010
Alternate JournalBrain Behav. Immun.
PubMed ID20854893
PubMed Central IDPMC3603145
Grant ListAG 026364 / AG / NIA NIH HHS / United States
CA116778 / CA / NCI NIH HHS / United States
HL 079955 / HL / NHLBI NIH HHS / United States
P30 AG028748 / AG / NIA NIH HHS / United States
P30-AG028748 / AG / NIA NIH HHS / United States
R01 CA116778 / CA / NCI NIH HHS / United States
RR00827 / RR / NCRR NIH HHS / United States
T32-MH19925 / MH / NIMH NIH HHS / United States