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A pilot study of blood epinephrine levels and CREB phosphorylation in men undergoing prostate biopsies

  • Urology - Original Paper
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Abstract

Purpose

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.

Conclusion

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.

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Acknowledgments

The authors are grateful to Karen Klein for critical reading and for helpful suggestions; to Denise Young for helping with patients’ recruitment and sample handling; and to Megan J. Whelan, Lisa Dixon, and Claire Kimbrough for IRB protocol assistance. Project described was supported by Award Number R01CA118329 from the National Cancer Institute to George Kulik. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

Conflict of interest

Authors declare no conflict of interest that pertains to this publication.

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Authors and Affiliations

  1. Department of Cancer Biology, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC, 27157, USA

    Sazzad Hassan, Yelena Karpova, Anabel Flores & George Kulik

  2. Comprehensive Cancer Center, Wake Forest University, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC, 27157, USA

    Ralph D’Agostino Jr. & George Kulik

  3. Social Sciences Health Policy, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC, 27157, USA

    Suzanne C. Danhauer

  4. Department of Urology, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC, 27157, USA

    Ashok Hemal & George Kulik

Authors
  1. Sazzad Hassan
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  2. Yelena Karpova
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  3. Anabel Flores
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  4. Ralph D’Agostino Jr.
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  5. Suzanne C. Danhauer
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  6. Ashok Hemal
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  7. George Kulik
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Corresponding author

Correspondence to George Kulik.

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Hassan, S., Karpova, Y., Flores, A. et al. A pilot study of blood epinephrine levels and CREB phosphorylation in men undergoing prostate biopsies. Int Urol Nephrol 46, 505–510 (2014). https://doi.org/10.1007/s11255-013-0513-0

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  • DOI: https://doi.org/10.1007/s11255-013-0513-0

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