Expression of the RET oncogene induces differentiation of SK-N-BE neuroblastoma cells

A. D'Alessio, G. De Vita, G. Cali, L. Nitsch, A. Fusco, G. Vecchio, G. Santelli, M. Santoro, V. De Franciscis

Research output: Contribution to journalArticlepeer-review

Abstract

Expression of the RET proto-oncogene, a cell surface receptor for an as yet unknown ligand, is associated with tumors, tissues, and cell lines of neural crest origin. Accumulating evidence suggests that RET activity is involved in the process of neuronal differentiation. Moreover, induction of phenotypic differentiation of neuroblastoma cell lines is associated with the rapid accumulation of RET transcripts. To verify the role of RET in neuronal differentiation, we introduced into the human neuroblastoma cell line SK-N- BE four versions of the RET oncogene, activated by different mechanisms: RET/PTC1 and RET/PTC3, which are activated by rearrangement with heterologous genes; and two activated RET mutants, which carry the single amino acid substitution found associated to the inheritance of the multiple endocrine neoplasia type 2A (retMEN2A allele) and type2B (retMEN2B allele), respectively. We demonstrate that, after transfection with the RET oncogenes, SK-N-BE cells display a reduced growth rate and acquire a neurite-bearing phenotype accompanied by enhanced expression of the axonal growth-associated protein, GAP-43, and the high molecular weight neurofilament, NF200. These results indicate that, when activated, RET is able to cause growth inhibition and to promote neuronal differentiation of neuroblastoma cells.

Original languageEnglish
Pages (from-to)1387-1394
Number of pages8
JournalCell Growth and Differentiation
Volume6
Issue number11
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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