Fibroblast growth factor-2 autofeedback regulation in pituitary folliculostellate TtT/GF cells

George Vlotides, Yen Hao Chen, Tamar Eigler, Song Guang Ren, Shlomo Melmed

Research output: Contribution to journalArticle

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Abstract

To investigate paracrine regulation of pituitary cell growth, we tested fibroblast growth factor (FGF) regulation of TtT/GF folliculostellate (FS) cells. FGF-2, and FGF-4 markedly induced cell proliferation, evidenced by induction of pituitary tumor transforming gene-1 (Pttg1) mRNA expression and percentage of cells in S phase. Signaling for FGF-2-induced FS cell proliferation was explored by specific pharmacological inhibition. A potent inhibitory effect on FGF-2 action was observed by blocking of Src tyrosine kinase with 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d] pyrimidine (≥0.1 μM), followed by protein kinase C (PKC) inhibition with GF109203X. Treatment with FGF-2 (30 ng/ml; 10 min) activated phosphorylation of signal transducer and activator of transcription-3, ERK, stress-activated protein kinase/c-Jun N-terminal kinase, Akt, and focal adhesion kinase. Src inhibition with 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d] pyrimidine suppressed FGF-2-induced Akt and focal adhesion kinase, indicating effects downstream of FGF-2-induced Src activation. FGF-2 also markedly induced its own mRNA expression, peaking at 2-4 h, and this effect was suppressed by Src tyrosine kinase inhibition. The PKC inhibitor GF109203X abolished FGF-2 autoinduction, indicating PKC as the primary pathway involved in FGF-2 autoregulation in these cells. In addition to pituitary FGF-2 paracrine activity on hormonally active cells, these results show an autofeedback mechanism for FGF-2 in non-hormone-secreting pituitary FS cells, inducing cell growth and its own gene expression, and mediated by Src/PKC signaling.

Original languageEnglish (US)
Pages (from-to)3252-3258
Number of pages7
JournalEndocrinology
Volume150
Issue number7
DOIs
StatePublished - Jul 1 2009

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Fibroblast Growth Factor 2
Protein Kinase C
src-Family Kinases
Focal Adhesion Protein-Tyrosine Kinases
Fibroblast Growth Factor 4
Cell Proliferation
STAT3 Transcription Factor
Messenger RNA
Fibroblast Growth Factors
Protein C Inhibitor
JNK Mitogen-Activated Protein Kinases
Pituitary Neoplasms
Protein Kinase Inhibitors
Growth
Heat-Shock Proteins
S Phase
Oncogenes
Protein Kinases
Homeostasis
Phosphorylation

ASJC Scopus subject areas

  • Endocrinology

Cite this

Fibroblast growth factor-2 autofeedback regulation in pituitary folliculostellate TtT/GF cells. / Vlotides, George; Chen, Yen Hao; Eigler, Tamar; Ren, Song Guang; Melmed, Shlomo.

In: Endocrinology, Vol. 150, No. 7, 01.07.2009, p. 3252-3258.

Research output: Contribution to journalArticle

Vlotides, G, Chen, YH, Eigler, T, Ren, SG & Melmed, S 2009, 'Fibroblast growth factor-2 autofeedback regulation in pituitary folliculostellate TtT/GF cells', Endocrinology, vol. 150, no. 7, pp. 3252-3258. https://doi.org/10.1210/en.2008-1625
Vlotides, George ; Chen, Yen Hao ; Eigler, Tamar ; Ren, Song Guang ; Melmed, Shlomo. / Fibroblast growth factor-2 autofeedback regulation in pituitary folliculostellate TtT/GF cells. In: Endocrinology. 2009 ; Vol. 150, No. 7. pp. 3252-3258.
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