The influence of heregulins on human Schwann cell proliferation

Allan D Levi, R. P. Bunge, J. A. Lofgren, L. Meima, F. Hefti, K. Nikolics, M. X. Sliwkowski

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Abstract

The use of Schwann cell (SC) autotransplantation to influence neural repair in humans is dependent upon identifying mitogens that will effectively expand human Schwann cells (SCs) in culture. The recent purification and molecular cloning of glial growth factor (GGF), a potent mitogen for rat Schwann cells, has led to the recognition that a family of proteins (GGF/HRG/NDF/ARIA) are alternatively spliced products of a single gene. The heregulins (HRGs) have been characterized with respect to their influence on human breast cancer cell lines; here we examined whether the HRGs have mitogenic activity for human SCs. Using DNA synthesis assays and serial passaging of cells in culture, we demonstrate that HRG is an effective mitogen for human SCs and that, in the presence of agents that elevate cAMP, it is possible to expand these cells over multiple passages without overwhelming fibroblast contamination. One putative target for this family of proteins is p185(erbB2), an EGF-like receptor tyrosine kinase that is encoded by the erbB2 protooncogene. In this report we also demonstrate that the erbB2/3/4 messages as well as the erbB2/3 receptor proteins are present within cultured human SCs. The addition of HRG to human SCs results in tyrosine phosphorylation of a 185 kDa protein. In the presence of stimulatory concentrations of HRG, a blocking monoclonal antibody (2C4) to p185(erbB2) is capable of significantly inhibiting phosphorylation of a 185 kDa protein as well as the subsequent incorporation of 3H-thymidine within the human SC. These latter results implicate an important role for p185(erbB2) in mediating the mitogenic response of human SCs to HRGs.

Original languageEnglish
Pages (from-to)1329-1340
Number of pages12
JournalJournal of Neuroscience
Volume15
Issue number2
StatePublished - Jan 1 1995

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Neuregulin-1
Schwann Cells
Cell Proliferation
Mitogens
Proteins
Cell Culture Techniques
Phosphorylation
Blocking Antibodies
Autologous Transplantation
Molecular Cloning
Epidermal Growth Factor Receptor
Human Activities
Protein-Tyrosine Kinases
Thymidine
Tyrosine
Fibroblasts
Monoclonal Antibodies
Breast Neoplasms
Cell Line

Keywords

  • cAMP
  • erbB2 receptor
  • heregulin
  • human
  • proliferation
  • Schwann cells

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Levi, A. D., Bunge, R. P., Lofgren, J. A., Meima, L., Hefti, F., Nikolics, K., & Sliwkowski, M. X. (1995). The influence of heregulins on human Schwann cell proliferation. Journal of Neuroscience, 15(2), 1329-1340.

The influence of heregulins on human Schwann cell proliferation. / Levi, Allan D; Bunge, R. P.; Lofgren, J. A.; Meima, L.; Hefti, F.; Nikolics, K.; Sliwkowski, M. X.

In: Journal of Neuroscience, Vol. 15, No. 2, 01.01.1995, p. 1329-1340.

Research output: Contribution to journalArticle

Levi, AD, Bunge, RP, Lofgren, JA, Meima, L, Hefti, F, Nikolics, K & Sliwkowski, MX 1995, 'The influence of heregulins on human Schwann cell proliferation', Journal of Neuroscience, vol. 15, no. 2, pp. 1329-1340.
Levi AD, Bunge RP, Lofgren JA, Meima L, Hefti F, Nikolics K et al. The influence of heregulins on human Schwann cell proliferation. Journal of Neuroscience. 1995 Jan 1;15(2):1329-1340.
Levi, Allan D ; Bunge, R. P. ; Lofgren, J. A. ; Meima, L. ; Hefti, F. ; Nikolics, K. ; Sliwkowski, M. X. / The influence of heregulins on human Schwann cell proliferation. In: Journal of Neuroscience. 1995 ; Vol. 15, No. 2. pp. 1329-1340.
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