A pilot study of blood epinephrine levels and CREB phosphorylation in men undergoing prostate biopsies.
OBJECTIVE
In mouse models of prostate cancer, increased epinephrine levels accelerated tumor growth via the beta2-adrenoreceptor/PKA signaling pathway. It is unknown, however, whether men experience increased epinephrine levels sufficient to activate the beta2-adrenoreceptor/PKA pathway in the prostate gland. We measured epinephrine levels in blood samples collected immediately prior to prostate biopsies and measured phosphorylation of S133CREB (PKA site), S112BAD, T202/Y204ERK, and S473 Akt in prostate biopsy tissue samples.


METHODS
Tissue samples and 3 ml of blood were obtained from men (n = 20) recruited from the patients scheduled for prostate biopsies. Epinephrine levels were measured by ELISA. Proteins were extracted from biopsied tissue, and protein phosphorylation was measured by Western blotting with phospho-specific antibodies. Pearson and Spearman's rank correlations were analyzed to assess relationships between blood epinephrine levels and phosphorylation of CREB, BAD, AKT, and ERK.


RESULTS
Epinephrine levels above 1 nM were detected in 5 of 20 patients. A strong positive correlation was observed between increased epinephrine levels and CREB phosphorylation. In contrast, no correlation was observed between epinephrine levels and phosphorylation of ERK, BAD, or AKT.


CONCLUSIONS
Our results suggest that increased blood epinephrine levels activate the beta2-adrenoreceptor/PKA signaling pathway in human prostate glands. These results will inform future studies to examine whether beta2-selective blockers can inhibit activation of the epinephrine/ADRB2/PKA pathway in prostate tumors of men with increased epinephrine levels and explore the use of beta2-selective blockers as adjuvant therapy for prostate cancer.
Department of Cancer Biology, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC, 27157, USA.
Sazzad
S
Hassan
Yelena
Y
Karpova
Anabel
A
Flores
Ralph
R
D'Agostino
Suzanne C
SC
Danhauer
Ashok
A
Hemal
George
G
Kulik
D000368:Aged; D001706:Biopsy; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004837:Epinephrine / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D010865:Pilot Projects; D011467:Prostate / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology
C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D004837:Epinephrine