The inhibitory effect of norepinephrine on the migration of ES-2 ovarian carcinoma cells involves a Rap1-dependent pathway.
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.
Institute of Immunology, Witten/Herdecke University, Stockumer Str. 10, 58448 Witten, Germany.
Philipp
P
Bastian
Agnieszka
A
Balcarek
Christina
C
Altanis
Carina
C
Strell
Bernd
B
Niggemann
Kurt S
KS
Zaenker
Frank
F
Entschladen
D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D009638:Norepinephrine / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000473:pathology*; D034622:RNA Interference; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism*
D000242:Cyclic AMP; D010738:Type C Phospholipases; D020827:rap1 GTP-Binding Proteins; D009638:Norepinephrine