Neurotensin regulates growth of human pancreatic cancer.
OBJECTIVE
The effect of neurotensin (NT) on in vitro-growth of human pancreatic cancer cells (MIA PaCa-2) was examined. Furthermore, the intracellular signal-transduction pathways by which neurotensin regulates growth of MIA PaCa-2 cells were determined.


BACKGROUND
NT is trophic for normal rat pancreas, but the effect of NT on growth of human pancreatic cancer is not known.


METHODS
Effects of NT (10(-12) to 10(-6) mol/l) on growth of MIA PaCa-2 cells were determined by both count of cell numbers and 3H-thymidine incorporation. Action of NT on phosphatidylinositol (PI) hydrolysis, cyclic AMP production, and intracellular calcium level were determined by conventional methods. The effects of 8-bromo-cyclic AMP and prostaglandin E2 on cell growth were determined.


RESULTS
Low concentrations of NT (10(-12) to 10(-9) mol/l) stimulated growth in a dose-dependent manner, but higher concentrations of NT (10(-8) to 10(-6) mol/l) did not stimulate growth of MIA PaCa-2 cells. NT (10(-12) to 10(-6) mol/l) stimulated PI hydrolysis and increased intracellular calcium levels in a dose-dependent manner. High concentrations of NT (10(-8) to 10(-6) mol/l) stimulated production of cyclic AMP in a dose-dependent manner. 8-bromo-cyclic AMP inhibited growth of MIA PaCa-2 cells; prostaglandin E2 did not affect growth of MIA PaCa-2 cells.


CONCLUSIONS
NT stimulates growth of MIA PaCa-2 cells through stimulation of PI hydrolysis and mobilization of calcium. Stimulation of the cyclic AMP pathway by high concentrations of NT abolishes the growth-stimulatory effect of NT that is mediated through PI hydrolysis or calcium mobilization.
Ishizuka
J
J
Department of Surgery, University of Texas Medical Branch, Galveston.
Townsend
C M
CM
Thompson
J C
JC
D002118:Calcium / Q000502:physiology; D002455:Cell Division; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000096:biosynthesis; D006801:Humans; D006868:Hydrolysis; D009496:Neurotensin / Q000494:pharmacology* / Q000502:physiology; D010190:Pancreatic Neoplasms / Q000473:pathology* / Q000503:physiopathology; D010716:Phosphatidylinositols / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D010716:Phosphatidylinositols; D009496:Neurotensin; D000242:Cyclic AMP; D002118:Calcium