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

L O Murphy; M W Cluck; S Lovas; F Otvös; R F Murphy; A V Schally; J Permert; J Larsson; J A Knezetic; T E Adrian

doi:10.1054/bjoc.2001.1698

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

Br J Cancer. 2001 Apr 6;84(7):926-35. doi: 10.1054/bjoc.2001.1698.

Authors

L O Murphy¹, M W Cluck, S Lovas, F Otvös, R F Murphy, A V Schally, J Permert, J Larsson, J A Knezetic, T E Adrian

Affiliation

¹ Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE 68178, USA.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Division / physiology
Culture Media, Serum-Free
Enzyme Activation
Enzyme Inhibitors / pharmacology
Epidermal Growth Factor / metabolism
ErbB Receptors / metabolism
ErbB Receptors / physiology*
Flavonoids / pharmacology
Gastrin-Releasing Peptide / metabolism
Gene Expression Regulation, Neoplastic
Humans
Insulin-Like Growth Factor I / metabolism
MAP Kinase Signaling System / physiology
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 Neoplasms / metabolism
Pancreatic Neoplasms / pathology*
Quinazolines
Substrate Specificity
Transcription Factor AP-1 / biosynthesis
Transcription Factor AP-1 / genetics
Tumor Cells, Cultured
Tyrphostins / pharmacology

Substances

Culture Media, Serum-Free
Enzyme Inhibitors
Flavonoids
Quinazolines
Transcription Factor AP-1
Tyrphostins
RTKI cpd
Epidermal Growth Factor
Insulin-Like Growth Factor I
Gastrin-Releasing Peptide
ErbB Receptors
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one