Neurotensin and EGF induce synergistic stimulation of DNA synthesis by increasing the duration of ERK signaling in ductal pancreatic cancer cells

Journal of Cellular Physiology
Krisztina KisfalviEnrique Rozengurt

Abstract

Neurotensin (NT) and epidermal growth factor (EGF) induced rapid extracellular-regulated protein kinase (ERK) activation through different signaling pathways in the K-Ras mutated human pancreatic carcinoma cell lines PANC-1 and MIA PaCa-2. NT stimulated ERK activation via a protein kinase C (PKC)-dependent (but EGF receptor-independent) pathway in PANC-1 and MIA PaCa-2 cells, whereas EGF promoted ERK activation through a PKC-independent pathway in these cells. Concomitant stimulation of these cells with NT and EGF induced a striking increase in the duration of ERK pathway activation as compared with that obtained in cells treated with each agonist alone. Stimulation with NT + EGF promoted synergistic stimulation of DNA synthesis and anchorage-independent growth. Addition of the MEK inhibitor U0126, either prior to stimulation with NT + EGF or 2 h after stimulation with NT + EGF prevented the synergistic increase in DNA synthesis and suppressed the sustained phase of ERK activation. Furthermore, treatment with the selective PKC inhibitor GF-1 converted the sustained ERK activation in response to NT and EGF into a transient signal and also abrogated the synergistic increase in DNA synthesis. Collectively, our results suggest that...Continue Reading

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Citations

Mar 28, 2008·Purinergic Signalling·I Novak
Apr 15, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Enrique RozengurtKrisztina Kisfalvi
Mar 5, 2013·Biochemical and Biophysical Research Communications·Wade A KrugerPhilip Poronnik
May 10, 2011·Regulatory Peptides·Konstantinos Kalafatakis, Konstantinos Triantafyllou
Sep 21, 2010·Biochemical and Biophysical Research Communications·Steven H Young, Enrique Rozengurt
Jul 14, 2010·Biochemical Pharmacology·Sushovan GuhaEnrique Rozengurt
Jan 19, 2010·Journal of Cellular Physiology·Krisztina KisfalviEnrique Rozengurt
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Oct 16, 2019·European Journal of Pharmacology·Terry W MoodyRobert T Jensen

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