Regulation of proliferation-survival decisions is controlled by FGF1 secretion in retinal pigmented epithelial cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2000-10-05

AUTHORS

Marijke Bryckaert, Xavier Guillonneau, Christiane Hecquet, Paolo Perani, Yves Courtois, Frederic Mascarelli

ABSTRACT

Fibroblast growth factor 1 (FGF1) induces proliferation and differentiation in a wide variety of cells of mesodermal and neuroectodermal origin. FGF1 has no ‘classical’ signal sequence to direct its secretion, and there has been considerable debate concerning FGF1 secretion and its role in the biological activities of FGF1. We investigated the effects of FGF1 secretion and the signalling induced by signal peptide (SP)-containing FGF1 and SP-less FGF1, on the proliferation and the apoptosis in retinal pigmented epithelial (RPE) cells. Primary RPE cell cultures were transfected with FGF1 (FGF1 cells) and SP-FGF1 (SP-FGF1 cells) cDNAs. SP-FGF1 cells secreted large amount of FGF1 and actively proliferated, whereas FGF1 and control cells did not. Secreted FGF1 induced short-term activation of both FGFR1 and ERK2, which were required for cell proliferation. In contrast, SP-FGF1 cells stopped secreting FGF1 and died rapidly, if cultured in the absence of serum. Surprisingly, FGF1 cells, but not control cells, secreted FGF1 and were resistant to apoptosis induced by serum depletion. Secreted FGF1 induced long-term activation of FGFR1 and ERK2, which was necessary to induce a constant and high level of Bcl-x production, and to induce cell survival in FGF1 cells. Downregulation of ERK2 and Bcl-x increased apoptosis. Thus, the proliferation and survival activities of FGF1 depend on the secretion of FGF1 which is determined by the cell culture conditions. Cell proliferation was SP-dependent, whereas cell survival was not. The signal peptide controls the level and duration, ‘whispering or shouting’, of ERK2 activation cells which determines FGF1 biological function and may have important implications for anti-degenerative and anti-proliferative treatments. More... »

PAGES

4917-4929

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.onc.1203872

DOI

http://dx.doi.org/10.1038/sj.onc.1203872

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1015252847

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/11039909


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