Nerve growth factor regulates dopamine D2 receptor expression in prolactinoma cell lines via p75NGFR-mediated activation of nuclear factor-κB

Chiara Fiorentini, Nicoletta Guerra, Marco Facchetti, Alessandra Finardi, Laura Tiberio, Luisa Schiaffonati, Pierfranco Spano, Cristina Missale

Research output: Contribution to journalArticle

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Abstract

Two groups of prolactinoma cell lines were identified. One group (responder) expresses both D2 dopamine receptors and an autocrine loop mediated by nerve growth factor (NGF) and one group (nonresponder) lacks both D2 receptors and NGF production. D2 receptor expression in these cell lines is dependent on NGF. Indeed, NGF inactivation in responder cells decreases D2 receptor density, while NGF treatment induces D2 receptor expression in nonresponders. Here we show that inactivation of p75NGFR, but not of trkA, resulted in D2 receptor loss in responder cells and prevented D2 receptor expression induced by NGF in the nonresponder. Analysis of nuclear factor-κB (NF-κB) nuclear accumulation and binding to corresponding DNA consensus sequences indicated that in NGF-secreting responder cells, but not in nonresponders, NF-κB is constitutively activated. Moreover, NGF treatment of nonresponder cells induced both nuclear translocation and DNA binding activity of NF-κB complexes containing p50, p65/RelA, and cRel subunits, an effect prevented by anti-p75NGFR antibodies. Disruption of NF-κB nuclear translocation by SN50 remarkably impaired D2 receptor expression in responder cells and prevented D2 gene expression induced by NGF in nonresponders. These data indicate that in prolactinoma cells the effect of NGF on D2 receptor expression is mediated by p75NGFR in a trkA-independent way and that NGF stimulation of p75NGFR activates NF-κB, which is required for D2 gene expression. We thus suggest that NF-κB is a key transcriptional regulator of the D2 gene and that this mechanism may not be confined to pituitary tumors, but could also extend to other dopaminergic systems.

Original languageEnglish
Pages (from-to)353-366
Number of pages14
JournalMolecular Endocrinology
Volume16
Issue number2
DOIs
Publication statusPublished - 2002

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Prolactinoma
Dopamine D2 Receptors
Nerve Growth Factor
Cell Line
Nerve Growth Factor Receptors
Gene Expression
Consensus Sequence
Pituitary Neoplasms
Regulator Genes
Anti-Idiotypic Antibodies

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Nerve growth factor regulates dopamine D2 receptor expression in prolactinoma cell lines via p75NGFR-mediated activation of nuclear factor-κB. / Fiorentini, Chiara; Guerra, Nicoletta; Facchetti, Marco; Finardi, Alessandra; Tiberio, Laura; Schiaffonati, Luisa; Spano, Pierfranco; Missale, Cristina.

In: Molecular Endocrinology, Vol. 16, No. 2, 2002, p. 353-366.

Research output: Contribution to journalArticle

Fiorentini, C, Guerra, N, Facchetti, M, Finardi, A, Tiberio, L, Schiaffonati, L, Spano, P & Missale, C 2002, 'Nerve growth factor regulates dopamine D2 receptor expression in prolactinoma cell lines via p75NGFR-mediated activation of nuclear factor-κB', Molecular Endocrinology, vol. 16, no. 2, pp. 353-366. https://doi.org/10.1210/me.16.2.353
Fiorentini, Chiara ; Guerra, Nicoletta ; Facchetti, Marco ; Finardi, Alessandra ; Tiberio, Laura ; Schiaffonati, Luisa ; Spano, Pierfranco ; Missale, Cristina. / Nerve growth factor regulates dopamine D2 receptor expression in prolactinoma cell lines via p75NGFR-mediated activation of nuclear factor-κB. In: Molecular Endocrinology. 2002 ; Vol. 16, No. 2. pp. 353-366.
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