HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 19, 14094-14100, May 11, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/19/14094    most recent M611370200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sastry, K. S. R. Articles by Kulik, G. Search for Related Content PubMed PubMed Citation Articles by Sastry, K. S. R. Articles by Kulik, G. Social Bookmarking                      What's this?

Epinephrine Protects Cancer Cells from Apoptosis via Activation of cAMP-dependent Protein Kinase and BAD Phosphorylation^*

Konduru S. R. Sastry, Yelena Karpova, Sergey Prokopovich, Adrienne J. Smith, Brian Essau, Avynash Gersappe¹, Jonathan P. Carson², Michael J. Weber, Thomas C. Register^¶, Yong Q. Chen, Raymond B. Penn^||, and George Kulik³

From the Department of Cancer Biology, ^¶Department of Pathology, Section on Comparative Medicine, and ^||Center for Human Genomics, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157 and the Department of Microbiology, University of Virginia, Charlottesville, Virginia 22908

The stress hormone epinephrine is known to elicit multiple systemic effects that include changes in cardiovascular parameters and immune responses. However, information about its direct action on cancer cells is limited. Here we provide evidence that epinephrine reduces sensitivity of cancer cells to apoptosis through interaction with ₂-adrenergic receptors. The antiapoptotic mechanism of epinephrine primarily involves phosphorylation and inactivation of the proapoptotic protein BAD by cAMP-dependent protein kinase. Moreover, BAD phosphorylation was observed at epinephrine concentrations found after acute and chronic psychosocial stress. Antiapoptotic signaling by epinephrine could be one of the mechanisms by which stress promotes tumorigenesis and decreases the efficacy of anti-cancer therapies.

Received for publication, December 12, 2006 , and in revised form, March 5, 2007.

^* This work was supported by United States Department of Defense Grant DAMD17-02-1-0154, Grants from the Comprehensive Cancer Center, and Wake Forest University School of Medicine Interim Funding (to G. K.) and National Institutes of Health Grant HL58506 (to R. P.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S3.

¹ Present address: BearingPoint Inc., 8725 W. Higgins Rd. Suites, Chicago, IL 60631.

² Present address: Center for Molecular Imaging Research, Harvard University, Charlestown, MA 02129.

³ To whom correspondence should be addressed: Dept. of Cancer Biology, Wake Forest University School of Medicine, Winston Salem, NC 27157. Tel.: 336-713-7650; Fax: 336-713-7661; E-mail: gkulik{at}wfubmc.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K. D. Sorensen, P. J. Wild, A. Mortezavi, K. Adolf, N. Torring, S. Heeboll, B. P. Ulhoi, P. Ottosen, T. Sulser, T. Hermanns, et al. Genetic and Epigenetic SLC18A2 Silencing in Prostate Cancer Is an Independent Adverse Predictor of Biochemical Recurrence after Radical Prostatectomy Clin. Cancer Res., February 15, 2009; 15(4): 1400 - 1410. [Abstract] [Full Text] [PDF]