Depression, social support, and beta-adrenergic transcription control in human ovarian cancer.
Motivated by previous indications that beta-adrenergic signaling can regulate tumor cell gene expression in model systems, we sought to determine whether similar dynamics occur in primary human ovarian cancer. DNA microarray analyses of 10 ovarian carcinomas identified 266 human transcripts that were differentially expressed in tumors from patients with elevated biobehavioral risk factors (high depressive symptoms and low social support) relative to grade- and stage-matched tumors from low-risk patients. Promoter-based bioinformatic analyses indicated increased activity of several beta-adrenergically-linked transcription control pathways, including CREB/ATF, NF-kappaB/Rel, STAT, and Ets family transcription factors. Consistent with increased beta-adrenergic signaling, high biobehavioral risk patients also showed increased intra-tumor concentrations of norepinephrine (but no difference in plasma norepinephrine). These data show that genome-wide transcriptional profiles are significantly altered in tumors from patients with high behavioral risk profiles, and they identify beta-adrenergic signal transduction as a likely mediator of those effects.
Department of Psychology, University of Iowa, USA.
Susan K
SK
Lutgendorf
Koen
K
DeGeest
Caroline Y
CY
Sung
Jesusa M
JM
Arevalo
Frank
F
Penedo
Joseph
J
Lucci
Michael
M
Goodheart
David
D
Lubaroff
Donna M
DM
Farley
Anil K
AK
Sood
Steve W
SW
Cole
D051696:Activating Transcription Factors / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002851:Chromatography, High Pressure Liquid; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D003863:Depression / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012944:Social Support; D014158:Transcription, Genetic
D051696:Activating Transcription Factors; D017362:Cyclic AMP Response Element-Binding Protein; D016328:NF-kappa B; D009638:Norepinephrine