Molecular Neurobiology

, Volume 15, Issue 3, pp 257–283

Growth factor regulation of cell growth and proliferation in the nervous system

A new intracrine nuclear mechanism
  • M. K. Stachowiak
  • J. Moffett
  • P. Maher
  • J. Tucholski
  • E. K. Stachowiak
Article

DOI: 10.1007/BF02740663

Cite this article as:
Stachowiak, M.K., Moffett, J., Maher, P. et al. Mol Neurobiol (1997) 15: 257. doi:10.1007/BF02740663

Abstract

This article discusses a novel intracrine mechanism of growth-factor action in the nervous system whereby fibroblast growth factor-2 (FGF-2) and its receptor accumulate in the cell nucleus and act as mediators in the control of cell growth and proliferation. In human and rat brain the levels and subcellular localization of FGF-2 differ between quiescent and reactive astrocytes. Quiescent cells express a low level of FGF-2, which is located predominantly within the cytoplasm. In reactive astrocytes, the expression of FGF-2 increases and the proteins are found in both the cytoplasm and nucleus. In glioma tumors, FGF-2 is overexpressed in the nuclei of neoplastic cells. Similar changes in FGF-2 expression and localization are found in vitro. The nuclear accumulation of FGF-2 reflects a transient activation of the FGF-2 gene by potentially novel transactivating factors interacting with an upstream regulatory promoter region. In parallel with FGF-2, the nuclei of astrocytes contain the high-affinity FGF-2 receptor, FGFR1. Nuclear FGFR1 is full length, retains kinase activity, and is localized within the nuclear interior in association with the nuclear matrix. Transfection of either FGF-2 or FGFR1 into cells that do not normally express these proteins results in their nuclear accumulation and concomitant increases in cell proliferation. A similar regulation of nuclear FGF-2 and FGFR1 is observed in neural crest-derived adrenal medullary cells and of FGF-2 in the nuclei of cerebellar neurons. Thus, the regulation of the nuclear content of FGF-2 and FGFR1 could serve as a novel mechanism controlling growth and proliferation of glial and neuronal cells.

Index Entries

FGF-2 FGF receptor nuclear localization cell plasticity astrocytes glioma cells 

Copyright information

© Humana Press Inc 1997

Authors and Affiliations

  • M. K. Stachowiak
    • 1
  • J. Moffett
    • 1
  • P. Maher
    • 2
  • J. Tucholski
    • 1
  • E. K. Stachowiak
    • 1
  1. 1.Laboratory of Molecular NeurobiologyBarrow Neurological InstitutePhoenix
  2. 2.The Scripps Research InstituteLa Jolla
  3. 3.Department of MicrobiologyUniversity of GdanskGdanskPoland