Selective regulation of TrkA and TrkB receptors by retinoic acid and interferon-γ in human neuroblastoma cell lines

E. Lucarelli, D. R. Kaplan, C. J. Thiele

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Trk receptors are a family of genes implicated in the survival, differentiation, and growth of certain neurons and tumors of the nervous system. A better understanding of the regulation of Trk receptors is relevant for developmental and oncological studies. Human neuroblastoma (NB) cell lines constitutively express low levels of TrkA mRNA, while TrkB mRNA is not readily detectable. Differentiation of NB cells is accompanied by a differential modulation of Trk expression in human NB cells. Nanomolar concentrations of RA induce a stable increase of TrkB mRNA. A transient induction of TrkA mRNA levels requires micromolar concentrations of RA. Induction of both TrkA and TrkB mRNA does not require new protein synthesis. However, RA-induced TrkB mRNA expression is transcriptionally regulated, while the transient RA-induced increase of TrkA mRNA is a consequence of extended mRNA stability. Interferon γ (IFN-γ) selectively increases TrkA mRNA without affecting TrkB mRNA levels. Similar to RA, IFN-γ does not modify the transcriptional rate of TrkA mRNA, but rather increases TrkA mRNA stability. Thus, RA and IFN-γ differentially regulate TrkA or TrkB expression in the same cell type by predominantly transcriptional (TrkB) or post transcriptional (TrkA) mechanisms. Such experiments indicate the complexity of Trk mRNA regulation and also indicate compounds that may affect neurotrophin responsiveness in developing neural cells.

Original languageEnglish
Pages (from-to)24725-24731
Number of pages7
JournalJournal of Biological Chemistry
Volume270
Issue number42
DOIs
Publication statusPublished - 1995

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trkA Receptor
trkB Receptor
Tretinoin
Neuroblastoma
Interferons
Cells
Cell Line
Messenger RNA
RNA Stability
Nervous System Neoplasms
Nerve Growth Factors
Neurology
Cell Differentiation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Selective regulation of TrkA and TrkB receptors by retinoic acid and interferon-γ in human neuroblastoma cell lines. / Lucarelli, E.; Kaplan, D. R.; Thiele, C. J.

In: Journal of Biological Chemistry, Vol. 270, No. 42, 1995, p. 24725-24731.

Research output: Contribution to journalArticle

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