Concomitant cell growth and differentiation are dependent on erbB1 and integrin activation in an autonomously surviving colon adenocarcinoma: involvement of autocrine amphiregulin secretion.

2.50
Hdl Handle:
http://hdl.handle.net/10541/72544
Title:
Concomitant cell growth and differentiation are dependent on erbB1 and integrin activation in an autonomously surviving colon adenocarcinoma: involvement of autocrine amphiregulin secretion.
Authors:
Picihard, Veronique; Berthois, Yolande; Roccabianca, Monique; Prévôt, Charles; Sarrazin, Marcel; Portugal, Henri; Kumar, Shant; Kumar, Patricia; Rognoni, Jean-Baptiste
Abstract:
In normal colon epithelium, cell proliferation is followed by cell differentiation. The purpose of this work was to investigate, in the HT29-D4 colon adenocarcinoma cell line, the occurrence of a temporal sequence of changes in cell proliferation and differentiation, the role of autocrine EGF family ligands and to determine which transduction pathway(s) are involved in these processes. In a medium lacking both growth factor and serum, HT29-D4 cells secreted amphiregulin (AR), which was shown to be strongly involved in cell adhesion, growth and differentiation. In the main, integrins alpha2beta1 and alphavbeta6 intervened in these processes. Using tyrphostins, it was demonstrated that AR involvement was mediated through the ErbB1/ERK1,2 and ErbB1/FAK pathways. These signalling molecules were directly involved in pRb inhibition and, thus, in cyclin A expression. Concomitantly, colon differentiation markers were also expressed. Furthermore, terminal cell maturation resulted in a colon absorptive cell with strong polarisation, the growth of which was inhibited by tyrphostin and an ERK1,2 inhibitor. It was concluded that in a colon adenocarcinoma, cell proliferation and differentiation can occur concomitantly and that these deregulated processes are controlled by autocrine secretion through the ErbB1/ERK1,2 and FAK pathways.
Affiliation:
FRE CNRS 2737, Faculté de Pharmacie, Université Aix-Marseille II, 27 Bd Jean Moulin, 13385 Marseille, France.
Citation:
Concomitant cell growth and differentiation are dependent on erbB1 and integrin activation in an autonomously surviving colon adenocarcinoma: involvement of autocrine amphiregulin secretion., 26 (4B):2769-83 Anticancer Res.
Journal:
Anticancer Research
Issue Date:
2006
URI:
http://hdl.handle.net/10541/72544
PubMed ID:
16886596
Type:
Article
Language:
en
ISSN:
0250-7005
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorPicihard, Veronique-
dc.contributor.authorBerthois, Yolande-
dc.contributor.authorRoccabianca, Monique-
dc.contributor.authorPrévôt, Charles-
dc.contributor.authorSarrazin, Marcel-
dc.contributor.authorPortugal, Henri-
dc.contributor.authorKumar, Shant-
dc.contributor.authorKumar, Patricia-
dc.contributor.authorRognoni, Jean-Baptiste-
dc.date.accessioned2009-07-06T10:47:55Z-
dc.date.available2009-07-06T10:47:55Z-
dc.date.issued2006-
dc.identifier.citationConcomitant cell growth and differentiation are dependent on erbB1 and integrin activation in an autonomously surviving colon adenocarcinoma: involvement of autocrine amphiregulin secretion., 26 (4B):2769-83 Anticancer Res.en
dc.identifier.issn0250-7005-
dc.identifier.pmid16886596-
dc.identifier.urihttp://hdl.handle.net/10541/72544-
dc.description.abstractIn normal colon epithelium, cell proliferation is followed by cell differentiation. The purpose of this work was to investigate, in the HT29-D4 colon adenocarcinoma cell line, the occurrence of a temporal sequence of changes in cell proliferation and differentiation, the role of autocrine EGF family ligands and to determine which transduction pathway(s) are involved in these processes. In a medium lacking both growth factor and serum, HT29-D4 cells secreted amphiregulin (AR), which was shown to be strongly involved in cell adhesion, growth and differentiation. In the main, integrins alpha2beta1 and alphavbeta6 intervened in these processes. Using tyrphostins, it was demonstrated that AR involvement was mediated through the ErbB1/ERK1,2 and ErbB1/FAK pathways. These signalling molecules were directly involved in pRb inhibition and, thus, in cyclin A expression. Concomitantly, colon differentiation markers were also expressed. Furthermore, terminal cell maturation resulted in a colon absorptive cell with strong polarisation, the growth of which was inhibited by tyrphostin and an ERK1,2 inhibitor. It was concluded that in a colon adenocarcinoma, cell proliferation and differentiation can occur concomitantly and that these deregulated processes are controlled by autocrine secretion through the ErbB1/ERK1,2 and FAK pathways.en
dc.language.isoenen
dc.subjectCell Line Tumouren
dc.subjectColonic Canceren
dc.subject.meshAdenocarcinoma-
dc.subject.meshAlkaline Phosphatase-
dc.subject.meshAntigens, Neoplasm-
dc.subject.meshCell Adhesion-
dc.subject.meshCell Differentiation-
dc.subject.meshCell Growth Processes-
dc.subject.meshCell Line, Tumor-
dc.subject.meshCell Membrane-
dc.subject.meshColonic Neoplasms-
dc.subject.meshCyclins-
dc.subject.meshEnzyme Activation-
dc.subject.meshFocal Adhesion Kinase 1-
dc.subject.meshGlycoproteins-
dc.subject.meshHT29 Cells-
dc.subject.meshHumans-
dc.subject.meshIntegrin alpha2beta1-
dc.subject.meshIntegrins-
dc.subject.meshIntercellular Signaling Peptides and Proteins-
dc.subject.meshMicrofilament Proteins-
dc.subject.meshMitogen-Activated Protein Kinase 1-
dc.subject.meshMitogen-Activated Protein Kinase 3-
dc.subject.meshReceptor, Epidermal Growth Factor-
dc.subject.meshRetinoblastoma Protein-
dc.subject.meshSucrase-Isomaltase Complex-
dc.subject.meshTyrphostins-
dc.titleConcomitant cell growth and differentiation are dependent on erbB1 and integrin activation in an autonomously surviving colon adenocarcinoma: involvement of autocrine amphiregulin secretion.en
dc.typeArticleen
dc.contributor.departmentFRE CNRS 2737, Faculté de Pharmacie, Université Aix-Marseille II, 27 Bd Jean Moulin, 13385 Marseille, France.en
dc.identifier.journalAnticancer Researchen
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