Overexpression of activated neu/erbB2 initiates immortalization and malignant transformation of immature Schwann cells in vitro

Lawrence (Larry) Sherman, Jonathan P. Sleeman, Robert F. Hennigan, Peter Herrlich, Nancy Ratner

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The neu/erbB2 protooncogene is overexpressed in numerous human cancers and is mutationally activated in N-ethyl-N-nitrosourea (ENU)-induced rodent tumors of the Schwann cell lineage. We investigated whether expression of activated neu in Schwann cells is sufficient to initiate their immortalization and transformation. Clones of embryonic dorsal root ganglia cells infected with a retrovirus bearing activated neu (NID cells) were selected based on their expression of Schwann cell-specific markers. Compared to embryonic Schwann cells infected with a virus encoding empty vector, we found that NID cells have altered shapes and disorganized cytoskeletons, grow in the absence of growth factors required for normal Schwann cell survival and proliferation, and can be repeatedly passaged. Furthermore, NID cells are invasive in an in vitro matrix invasion assay and form metastatic tumors when injected into syngeneic animals. The neu-induced growth and invasive phenotypes could be reversed by drugs that inhibit Ras and Src activity. Interestingly, later stage Schwann cells infected with activated neu failed to become immortalized. These findings indicate that constitutive activation of erbB2 is sufficient to initiate the immortalization and transformation of immature Schwann cells, and support the notion that Schwann cells have particular developmental stages during which they are susceptible to immortalizing and transforming events.

Original languageEnglish (US)
Pages (from-to)6692-6699
Number of pages8
JournalOncogene
Volume18
Issue number48
StatePublished - Nov 18 1999
Externally publishedYes

Fingerprint

Schwann Cells
Ethylnitrosourea
Neoplasms
In Vitro Techniques
Spinal Ganglia
Cell Lineage
Retroviridae
Cytoskeleton
Rodentia
Cell Survival
Intercellular Signaling Peptides and Proteins
Clone Cells
Cell Proliferation
Viruses
Phenotype
Growth
Pharmaceutical Preparations

Keywords

  • erbB2
  • Immortalization
  • Neu
  • Schwann cells
  • Transformation

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Overexpression of activated neu/erbB2 initiates immortalization and malignant transformation of immature Schwann cells in vitro. / Sherman, Lawrence (Larry); Sleeman, Jonathan P.; Hennigan, Robert F.; Herrlich, Peter; Ratner, Nancy.

In: Oncogene, Vol. 18, No. 48, 18.11.1999, p. 6692-6699.

Research output: Contribution to journalArticle

Sherman, Lawrence (Larry) ; Sleeman, Jonathan P. ; Hennigan, Robert F. ; Herrlich, Peter ; Ratner, Nancy. / Overexpression of activated neu/erbB2 initiates immortalization and malignant transformation of immature Schwann cells in vitro. In: Oncogene. 1999 ; Vol. 18, No. 48. pp. 6692-6699.
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