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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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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O ; CLUCK, M. W ; LOVAS, S ; ÖTVÖS, F ; MURPHY, R. F ; SCHALLY, A. V ; PERMERT, J ; LARSSON, J ; KNEZETIC, J. A ; ADRIAN, T. E</creator><creatorcontrib>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</creatorcontrib><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.</description><identifier>ISSN: 0007-0920</identifier><identifier>ISSN: 1532-1827</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1054/bjoc.2001.1698</identifier><identifier>PMID: 11286473</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>Basingstoke: Nature Publishing Group</publisher><subject>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</subject><ispartof>British journal of cancer, 2001-04, Vol.84 (7), p.926-935</ispartof><rights>2001 INIST-CNRS</rights><rights>Copyright 2001 Cancer Research Campaign.</rights><rights>Copyright Nature Publishing Group Apr 2001</rights><rights>Copyright © 2001 Cancer Research Campaign 2001 Cancer Research Campaign</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c583t-6b41a30245f891b0ffbd103b7390750de0d62c3dfe3502c01b0de64474e386d53</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363846/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363846/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,554,729,782,786,887,2729,27931,27932,53798,53800</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1128640$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11286473$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:1956777$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>MURPHY, L. O</creatorcontrib><creatorcontrib>CLUCK, M. W</creatorcontrib><creatorcontrib>LOVAS, S</creatorcontrib><creatorcontrib>ÖTVÖS, F</creatorcontrib><creatorcontrib>MURPHY, R. F</creatorcontrib><creatorcontrib>SCHALLY, A. V</creatorcontrib><creatorcontrib>PERMERT, J</creatorcontrib><creatorcontrib>LARSSON, J</creatorcontrib><creatorcontrib>KNEZETIC, J. A</creatorcontrib><creatorcontrib>ADRIAN, T. E</creatorcontrib><title>Pancreatic cancer cells require an EGF receptor-mediated autocrine pathway for proliferation in serum-free conditions</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><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.</description><subject>Biological and medical sciences</subject><subject>Cell Division - physiology</subject><subject>Culture Media, Serum-Free</subject><subject>Enzyme Activation</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Epidermal Growth Factor - metabolism</subject><subject>ERK1 protein</subject><subject>ERK2 protein</subject><subject>Flavonoids - pharmacology</subject><subject>Gastrin-Releasing Peptide - metabolism</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Insulin-Like Growth Factor I - metabolism</subject><subject>Liver. Biliary tract. Portal circulation. 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O ; CLUCK, M. W ; LOVAS, S ; ÖTVÖS, F ; MURPHY, R. F ; SCHALLY, A. V ; PERMERT, J ; LARSSON, J ; KNEZETIC, J. A ; ADRIAN, T. E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c583t-6b41a30245f891b0ffbd103b7390750de0d62c3dfe3502c01b0de64474e386d53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Biological and medical sciences</topic><topic>Cell Division - physiology</topic><topic>Culture Media, Serum-Free</topic><topic>Enzyme Activation</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Epidermal Growth Factor - metabolism</topic><topic>ERK1 protein</topic><topic>ERK2 protein</topic><topic>Flavonoids - pharmacology</topic><topic>Gastrin-Releasing Peptide - metabolism</topic><topic>Gastroenterology. Liver. Pancreas. 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O</au><au>CLUCK, M. W</au><au>LOVAS, S</au><au>ÖTVÖS, F</au><au>MURPHY, R. F</au><au>SCHALLY, A. V</au><au>PERMERT, J</au><au>LARSSON, J</au><au>KNEZETIC, J. A</au><au>ADRIAN, T. E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pancreatic cancer cells require an EGF receptor-mediated autocrine pathway for proliferation in serum-free conditions</atitle><jtitle>British journal of cancer</jtitle><addtitle>Br J Cancer</addtitle><date>2001-04-06</date><risdate>2001</risdate><volume>84</volume><issue>7</issue><spage>926</spage><epage>935</epage><pages>926-935</pages><issn>0007-0920</issn><issn>1532-1827</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><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.</abstract><cop>Basingstoke</cop><pub>Nature Publishing Group</pub><pmid>11286473</pmid><doi>10.1054/bjoc.2001.1698</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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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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