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http://hdl.handle.net/2445/177013
Title: | Differentiation of lactotrope precursor GHFT cells in response to Fibroblast Growth Factor-2 |
Author: | López-Fernandez, Judith Palacios, Daniela Castillo, Ana I. Tolon, Rosa M. Aranda, Ana Karin, Michael |
Keywords: | Diferenciació cel·lular Prolactina Efectes secundaris dels medicaments Cell diferentiation Prolactin Drug side effects |
Issue Date: | 14-Jul-2000 |
Publisher: | American Society for Biochemistry and Molecular Biology |
Abstract: | The mechanisms that control the emergence of different anterior pituitary cells from a common stem cell population are largely unknown. The immortalized GHFT cells derived from targeted expression of SV40 T antigen to mouse pituitary display characteristics of somatolactotropic progenitors in that they express the transcription factor GHF-1 (Pit-1) but not growth hormone (GH) or prolactin (PRL). We searched for factors capable of inducing lactotropic differentiation of GHFT cells. PRL gene expression was not observed in cells subjected to a variety of stimuli, which induce PRL gene expression in mature lactotropes. Only fibroblast growth factor-2 (FGF-2) was able to initiate the transcription, synthesis, and release of PRL in GHFT cells. However, induction of PRL expression was incomplete in FGF-2-treated cells, suggesting that additional factors are necessary to attain high levels of PRL transcription in fully differentiated lactotropes. We also show that the FGF-2 response element is located in the proximal PRL promoter. Stimulation of PRL expression by FGF-2 requires endogenous Ets factors and these factors as well as GHF-1 are expressed at low levels in the committed precursor, suggesting that these low levels are limiting for full PRL expression. Moreover, FGF-2 effect on lactotrope differentiation is mediated, at least partially, by stimulation of the Ras-signaling pathway. Our results suggest that, indeed, GHFT cells represent a valid model for studying lactotropic differentiation and that FGF-2 could play a key role both in initiating lactotrope differentiation and maintaining PRL expression. |
Note: | Reproducció del document publicat a: https://doi.org/10.1074/jbc.M002129200 |
It is part of: | Journal of Biological Chemistry, 2000, vol. 275, num. 28, p. 21653-21660 |
URI: | http://hdl.handle.net/2445/177013 |
Related resource: | https://doi.org/10.1074/jbc.M002129200 |
ISSN: | 0021-9258 |
Appears in Collections: | Articles publicats en revistes (Ciències Clíniques) |
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