Depression, social support, and beta-adrenergic transcription control in human ovarian cancer

• DOI: 10.1016/j.bbi.2008.04.155
• Publication Date: 2008-06-12T14:05:56Z
• Authors: Susan K. Lutgendorf; Koen DeGeest; Caroline Y. Sung; Jesusa M. Arevalo; Frank Penedo; Joseph Lucci; Michael Goodheart; David Lubaroff; Donna M. Farley; Anil K. Sood; Steve W. Cole
• Keywords: Adult; Aged, 80 and over; Ovarian Neoplasms; Transcription, Genetic; Depression; Reverse Transcriptase Polymerase Chain Reaction; NF-kappa B; 1. No poverty; Social Support; Middle Aged; Activating Transcription Factors; 3. Good health; Gene Expression Regulation, Neoplastic; Norepinephrine; 03 medical and health sciences; 0302 clinical medicine; Risk Factors; Neoplasms; Humans; Female; Cyclic AMP Response Element-Binding Protein; Chromatography, High Pressure Liquid; Aged; Oligonucleotide Array Sequence Analysis

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.