Abstract
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-κB/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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 176-183 |
| Number of pages | 8 |
| Journal | Brain, Behavior, and Immunity |
| Volume | 23 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 2009 |
Funding
We thank Heena Maiseri, Stephanie McGinn, Vanessa Lehner, Cecilia Torres, and the UCLA DNA Microarray Core for technical assistance, and David Bender, Thomas Buekers, and Paige McDonald for their thoughtful discussions. Research supported by the National Cancer Institute (R21 CA88293, R01 CA104825, R01 CA109298, R01 CA110793, and R01 CA116778).
Keywords
- Beta-adrenergic receptor
- Gene expression
- Ovarian cancer
- Sympathetic nervous system
- Transcription factor
ASJC Scopus subject areas
- Endocrine and Autonomic Systems
- Behavioral Neuroscience
- Immunology
