Post-transcriptional silencing of RET occurs, but is not required, during raf-1 mediated differentiation of medullary thyroid carcinoma cells

Eleanor B. Carson-Walter, Darrin P. Smith, Bruce A.J. Ponder, Stephen B. Baylin, Barry D. Nelkin

Research output: Contribution to journalArticle

Abstract

Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor of the calcitonin secreting thyroid C-cells. Somatic and germline mutations in the RET proto-oncogene are associated with sporadic and inherited cases of MTC, respectively. The human MTC cell line, TT, can be differentiated by activated raf-1. This differentiation is characterized, in part, by down-regulation of the RET proto-oncogene. We now show that raf-1 induction is followed by activation of the downstream kinases MEK1/2 and ERK1/2 and that differentiation is dependent on activation of MEK1/2. The concurrent down-regulation of RET appears to involve altered nuclear compartmentalization and transport of RET mRNA. Although RET is down-regulated during raf-1 mediated differentiation, overexpression of activated RET alleles which resist down-regulation does not alter the raf-1 mediated differentiation response. These data suggest that RET down-regulation is associated with, but not required, for raf-1 mediated MTC cell differentiation and that the raf-1 signal transduction pathway plays a dominant role in promoting MTC cell differentiation.

Original languageEnglish (US)
Pages (from-to)367-376
Number of pages10
JournalOncogene
Volume17
Issue number3
DOIs
StatePublished - Jul 23 1998

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Keywords

  • Differentiation
  • RET
  • Raf-1

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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