A1 Refereed original research article in a scientific journal
Syndecan-1 regulates FGF8b responses in S115 mammary carcinoma cells
Authors: Viklund L, Vorontsova N, Henttinen T, Salmivirta M
Publisher: TAYLOR & FRANCIS LTD
Publication year: 2006
Journal:Growth Factors
Journal name in sourceGROWTH FACTORS
Journal acronym: GROWTH FACTORS
Volume: 24
Issue: 2
First page : 151
Last page: 157
Number of pages: 7
ISSN: 0897-7194
DOI: https://doi.org/10.1080/08977190600699426
Abstract
In murine mammary carcinoma cells Shionogi 115 (S115) testosterone induces phenotypical transformation which is largely due to expression of fibroblast growth factor (FGF) 8b. Concomitantly, the expression of the cell surface heparan sulfate proteoglycan syndecan-1 is down-regulated. However, if syndecan-1 expression is maintained by transfection with a testosterone-driven syndecan-1 construct, transformation does not occur. Here we have investigated how the down-regulation of syndecan-1 expression in testosterone-treated S115 cells and the high level of expression in syndecan-1 transfected cells influence the cellular responses toward FGF8b. Our results show that high level of syndecan-1 is associated with a decreased magnitude and duration of the FGF8b induced Erk phosphorylation. This effect was observed regardless whether the cells were stimulated directly with exogenous FGF8b or with testosterone to induce autocrine FGF8b production. Moreover, syndecan-1 transfected cells did not respond to FGF8b stimulation by increase in the intracellular free calcium, whereas untransfected cells displayed a rapid (10 s) induction. These data suggest that, in S115 cells, syndecan-1 acts as a modulator of FGF8b signaling that can limit cellular responses to FGF receptor activation. The decreased levels of syndecan-1 expression and upregulation of the FGF signaling system seen in many cancers may contribute to the proliferation of the malignant cells in vivo .
In murine mammary carcinoma cells Shionogi 115 (S115) testosterone induces phenotypical transformation which is largely due to expression of fibroblast growth factor (FGF) 8b. Concomitantly, the expression of the cell surface heparan sulfate proteoglycan syndecan-1 is down-regulated. However, if syndecan-1 expression is maintained by transfection with a testosterone-driven syndecan-1 construct, transformation does not occur. Here we have investigated how the down-regulation of syndecan-1 expression in testosterone-treated S115 cells and the high level of expression in syndecan-1 transfected cells influence the cellular responses toward FGF8b. Our results show that high level of syndecan-1 is associated with a decreased magnitude and duration of the FGF8b induced Erk phosphorylation. This effect was observed regardless whether the cells were stimulated directly with exogenous FGF8b or with testosterone to induce autocrine FGF8b production. Moreover, syndecan-1 transfected cells did not respond to FGF8b stimulation by increase in the intracellular free calcium, whereas untransfected cells displayed a rapid (10 s) induction. These data suggest that, in S115 cells, syndecan-1 acts as a modulator of FGF8b signaling that can limit cellular responses to FGF receptor activation. The decreased levels of syndecan-1 expression and upregulation of the FGF signaling system seen in many cancers may contribute to the proliferation of the malignant cells in vivo .
UTU Research Portal