Document Detail

Behavioral stress accelerates prostate cancer development in mice.
MedLine Citation:
PMID:  23348742     Owner:  NLM     Status:  MEDLINE    
Prostate cancer patients have increased levels of stress and anxiety. Conversely, men who take beta blockers, which interfere with signaling from the stress hormones adrenaline and noradrenaline, have a lower incidence of prostate cancer; however, the mechanisms underlying stress-prostate cancer interactions are unknown. Here, we report that stress promotes prostate carcinogenesis in mice in an adrenaline-dependent manner. Behavioral stress inhibited apoptosis and delayed prostate tumor involution both in phosphatase and tensin homolog-deficient (PTEN-deficient) prostate cancer xenografts treated with PI3K inhibitor and in prostate tumors of mice with prostate-restricted expression of c-MYC (Hi-Myc mice) subjected to androgen ablation therapy with bicalutamide. Additionally, stress accelerated prostate cancer development in Hi-Myc mice. The effects of stress were prevented by treatment with the selective β2-adrenergic receptor (ADRB2) antagonist ICI118,551 or by inducible expression of PKA inhibitor (PKI) or of BCL2-associated death promoter (BAD) with a mutated PKA phosphorylation site (BADS112A) in xenograft tumors. Effects of stress were also blocked in Hi-Myc mice expressing phosphorylation-deficient BAD (BAD3SA). These results demonstrate interactions between prostate tumors and the psychosocial environment mediated by activation of an adrenaline/ADRB2/PKA/BAD antiapoptotic signaling pathway. Our findings could be used to identify prostate cancer patients who could benefit from stress reduction or from pharmacological inhibition of stress-induced signaling.
Sazzad Hassan; Yelena Karpova; Daniele Baiz; Dana Yancey; Ashok Pullikuth; Anabel Flores; Thomas Register; J Mark Cline; Ralph D'Agostino; Nika Danial; Sandeep Robert Datta; George Kulik
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2013-01-25
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  123     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-04-19     Completed Date:  2013-05-13     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  874-86     Citation Subset:  AIM; IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Adrenergic beta-Antagonists / pharmacology
Cell Line, Tumor
Disease Models, Animal
Epinephrine / physiology
Hypothalamo-Hypophyseal System / physiopathology
Mice, Inbred BALB C
Mice, Nude
PTEN Phosphohydrolase / deficiency
Pituitary-Adrenal System / physiopathology
Propanolamines / pharmacology
Prostatic Neoplasms / etiology*,  pathology,  physiopathology,  psychology*
Proto-Oncogene Proteins c-myc / metabolism
Receptors, Adrenergic, beta-2 / metabolism
Signal Transduction
Stress, Psychological / complications*,  physiopathology
Transplantation, Heterologous
bcl-Associated Death Protein / genetics,  metabolism
Grant Support
P30 CA012197/CA/NCI NIH HHS; R01 CA118329/CA/NCI NIH HHS; R01CA118329/CA/NCI NIH HHS
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Bad protein, mouse; 0/Myc protein, mouse; 0/Propanolamines; 0/Proto-Oncogene Proteins c-myc; 0/Receptors, Adrenergic, beta-2; 0/bcl-Associated Death Protein; 72795-19-8/ICI 118551; EC protein, mouse; EC Phosphohydrolase; YKH834O4BH/Epinephrine
Comment In:
J Clin Invest. 2013 Feb 1;123(2):558-60   [PMID:  23348736 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  The LINC complex is essential for hearing.
Next Document:  Blockade of NOX2 and STIM1 signaling limits lipopolysaccharide-induced vascular inflammation.