Pancreatic cancer cells require an EGF receptor-mediated autocrine pathway for proliferation in serum-free conditions

In-vitro and in-vivo studies have shown that autocrine growth factors and receptors are frequently expressed in human malignancies. Few of these studies, however, provide evidence that the identified autocrine pathway is functional. In this study, a functional autocrine growth pathway in pancreatic...

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Veröffentlicht in:British journal of cancer 2001-04, Vol.84 (7), p.926-935
Hauptverfasser: MURPHY, L. O, CLUCK, M. W, LOVAS, S, ÖTVÖS, F, MURPHY, R. F, SCHALLY, A. V, PERMERT, J, LARSSON, J, KNEZETIC, J. A, ADRIAN, T. E
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container_end_page 935
container_issue 7
container_start_page 926
container_title British journal of cancer
container_volume 84
creator MURPHY, L. O
CLUCK, M. W
LOVAS, S
ÖTVÖS, F
MURPHY, R. F
SCHALLY, A. V
PERMERT, J
LARSSON, J
KNEZETIC, J. A
ADRIAN, T. E
description In-vitro and in-vivo studies have shown that autocrine growth factors and receptors are frequently expressed in human malignancies. Few of these studies, however, provide evidence that the identified autocrine pathway is functional. In this study, a functional autocrine growth pathway in pancreatic cancer has been identified using an in-vitro cell culture system. When pancreatic cancer cells were grown without change of medium, proliferation was greater than when either medium was replaced frequently (HPAF, CAPAN-2, PANC-1 or SW1990) or cells were grown in the presence of the EGF receptor tyrosine kinase inhibitor AG1478 or the MEK inhibitor PD098059 (HPAF or CAPAN-2). Activity of extracellular-regulated kinases (ERK) 1 and 2 and c- jun and c- fos mRNA levels were significantly elevated in CAPAN-2 cells cultured continuously in serum-free medium. Collectively, the observations indicate that the EGF receptor and the ERK MAP kinase pathway mediate autocrine signals. In contrast to previous reports, the GRP and IGF-I receptors were shown not to be required for autocrine effects on pancreatic cancer cell proliferation. Autocrine stimulation of the EGF receptor can contribute to sustained mitogenic activity and proliferation of pancreatic cancer cells.
doi_str_mv 10.1054/bjoc.2001.1698
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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SWEPUB Freely available online; Nature Journals Online; PubMed Central
subjects Biological and medical sciences
Cell Division - physiology
Culture Media, Serum-Free
Enzyme Activation
Enzyme Inhibitors - pharmacology
Epidermal Growth Factor - metabolism
ERK1 protein
ERK2 protein
Flavonoids - pharmacology
Gastrin-Releasing Peptide - metabolism
Gastroenterology. Liver. Pancreas. Abdomen
Gene Expression Regulation, Neoplastic
Humans
Insulin-Like Growth Factor I - metabolism
Liver. Biliary tract. Portal circulation. Exocrine pancreas
MAP Kinase Signaling System - physiology
Medical sciences
Medicin och hälsovetenskap
Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors
Mitogen-Activated Protein Kinase 1 - metabolism
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases - antagonists & inhibitors
Mitogen-Activated Protein Kinases - metabolism
Pancreatic cancer
Pancreatic Neoplasms - metabolism
Pancreatic Neoplasms - pathology
Quinazolines
Receptor, Epidermal Growth Factor - metabolism
Receptor, Epidermal Growth Factor - physiology
Regular
Substrate Specificity
Transcription Factor AP-1 - biosynthesis
Transcription Factor AP-1 - genetics
Tumor Cells, Cultured
Tumors
Tyrphostins - pharmacology
title Pancreatic cancer cells require an EGF receptor-mediated autocrine pathway for proliferation in serum-free conditions
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