Differentiation of lactotrope precursor GHFT cells in response to fibroblast growth factor-2

Judith López-Fernández, Daniela Palacios, Ana I. Castillo, Rosa M. Tolón, Ana Aranda, Michael Karin

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 commitred 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.

Original languageEnglish
Pages (from-to)21653-21660
Number of pages8
JournalJournal of Biological Chemistry
Volume275
Issue number28
DOIs
Publication statusPublished - Jul 14 2000

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Fibroblast Growth Factor 2
Prolactin
Transcription
Gene expression
Transcription Factor Pit-1
Polyomavirus Transforming Antigens
Gene Expression
Response Elements
Stem cells
Growth Hormone
Cell Differentiation
Stem Cells
Display devices
Cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

Differentiation of lactotrope precursor GHFT cells in response to fibroblast growth factor-2. / López-Fernández, Judith; Palacios, Daniela; Castillo, Ana I.; Tolón, Rosa M.; Aranda, Ana; Karin, Michael.

In: Journal of Biological Chemistry, Vol. 275, No. 28, 14.07.2000, p. 21653-21660.

Research output: Contribution to journalArticle

López-Fernández, J, Palacios, D, Castillo, AI, Tolón, RM, Aranda, A & Karin, M 2000, 'Differentiation of lactotrope precursor GHFT cells in response to fibroblast growth factor-2', Journal of Biological Chemistry, vol. 275, no. 28, pp. 21653-21660. https://doi.org/10.1074/jbc.M002129200
López-Fernández, Judith ; Palacios, Daniela ; Castillo, Ana I. ; Tolón, Rosa M. ; Aranda, Ana ; Karin, Michael. / Differentiation of lactotrope precursor GHFT cells in response to fibroblast growth factor-2. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 28. pp. 21653-21660.
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