The inhibitory effect of norepinephrine on the migration of ES-2 ovarian carcinoma cells involves a Rap1-dependent pathway

Cancer Lett. 2009 Feb 18;274(2):218-24. doi: 10.1016/j.canlet.2008.09.008. Epub 2008 Oct 11.

Abstract

Our previous studies have shown that norepinephrine induces the migratory activity of human PC-3 prostate, SW 480 colon and MDA-MB-468 breast carcinoma cells. In contrast to these results, we show here that human ES-2 ovarian carcinoma cells have a reduced migratory activity after norepinephrine treatment. This inhibitory effect is possibly mediated by a cAMP-dependent activation of the small GTPase Rap1 via Epac. Furthermore, a key signalling event of the promigratory effect of norepinephrine in the above mentioned carcinoma cells is the activation of phospholipase C enzymes. In ES-2 cells, this part of the signalling cascade is constitutively active.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cyclic AMP / metabolism
  • Enzyme Activation
  • Female
  • Flow Cytometry
  • Humans
  • Norepinephrine / pharmacology*
  • Ovarian Neoplasms / enzymology
  • Ovarian Neoplasms / pathology*
  • RNA Interference
  • Signal Transduction
  • Type C Phospholipases / metabolism
  • rap1 GTP-Binding Proteins / metabolism*

Substances

  • Cyclic AMP
  • Type C Phospholipases
  • rap1 GTP-Binding Proteins
  • Norepinephrine