β-arrestin2 Mediates β-2 Adrenergic Receptor Signaling Inducing Prostate Cancer Cell Progression

Oncol Rep. 2011 Dec;26(6):1471-7. doi: 10.3892/or.2011.1417. Epub 2011 Aug 10.

Abstract

The expression of the β-2 adrenergic receptor (β2AR), one of the stress-inducible receptors, has been reported to be closely correlated with malignant tumors. Prostate cancer is the most common non-cutaneous cancer among males, accompanied with increased castration levels and β2AR activation in patients. However, the role of β2AR activation in prostate cancer cells and its underlying mechanisms are not fully understood. Here, we found that β2AR activation promoted cell proliferation and cell migration through increasing cellular adenylyl cyclase (cAMP) levels and ERK1/2 activation in LNCaP and PC3 prostate cancer cells. Moreover, the scaffold protein β-arrestin2 was found to be involved in the β2AR-mediated activation of ERK1/2 and cell proliferation using stable overexpressing β-arrestin2 LNCaP (LNCaP-βArr2) cells. Furthermore, enhanced β-arrestin2/c-Src complex formation by β2AR activation was observed in LNCaP-βArr2 cells. In addition, the c-Src inhibitor could block this enhanced complex formation and suppressed cell proliferation. This study demonstrates that βArr2 is involved in prostate carcinogenesis induced by stress and provides potential therapeutic targets for cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-2 Receptor Agonists / pharmacology
  • Arrestins / metabolism*
  • CSK Tyrosine-Protein Kinase
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation*
  • Cell Survival
  • Cyclic AMP / metabolism
  • Enzyme Activation
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Isoproterenol / pharmacology
  • Male
  • Prostatic Neoplasms
  • Protein Binding
  • Protein Transport
  • Protein-Tyrosine Kinases / metabolism
  • Receptors, Adrenergic, beta-2 / metabolism*
  • Signal Transduction*
  • Stress, Psychological
  • beta-Arrestins
  • src-Family Kinases

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Arrestins
  • Receptors, Adrenergic, beta-2
  • beta-Arrestins
  • Cyclic AMP
  • Protein-Tyrosine Kinases
  • CSK Tyrosine-Protein Kinase
  • src-Family Kinases
  • CSK protein, human
  • Extracellular Signal-Regulated MAP Kinases
  • Isoproterenol