Concomitant cell growth and differentiation are dependent on erbB1 and integrin activation in an autonomously surviving colon adenocarcinoma: involvement of autocrine amphiregulin secretion.
Picihard, Veronique Berthois, Yolande Roccabianca, Monique Prévôt, Charles Sarrazin, Marcel Portugal, Henri Kumar, Shant Kumar, Patricia Rognoni, Jean-Baptiste
Picihard, Veronique
Berthois, Yolande
Roccabianca, Monique
Prévôt, Charles
Sarrazin, Marcel
Portugal, Henri
Kumar, Shant
Kumar, Patricia
Rognoni, Jean-Baptiste
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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.
Description
Date
2006
Publisher
Collections
Keywords
Cell Line Tumour
Colonic Cancer
Colonic Cancer
Type
Article
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.