RET activation inhibits doxorubicin-induced apoptosis in SK-N-MC cells

Michael A. Skinner, Karen E. Lackey, Alex J. Freemerman

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Background: Medullary thyroid cancer (MTC) is generally resistant to chemotherapy and the frequent constitutive activation of RET (rearranged during transfection gene) in these tumors might inhibit drug-induced apoptosis. Materials and Methods: Each RET isoform was separately expressed in SK-N-MC cells (neural crest-derived tumor) and the impact of RET activation on doxorubicin-induced apoptosis was examined. Results: The activation of RET9 and RET51 in the SK-N-MC cells significantly reduced the doxorubicin-induced apoptosis by 50%, compared to untreated cells. RET activation also induced phosphorylation of ERK (extracellular regulated kinase), but no changes in AKT (serine/threonine kinase) phosphorylation were noted. In the presence of a MAP (mitogen-activated protein) kinase inhibitor or a RET kinase inhibitor, the RET-activated/drug-treated cells displayed nearly 75% and 100% of the doxorubicin-induced apoptosis of the drug-treated cells without RET activation, respectively. Conclusion: In SK-N-MC cells, downstream activation of MAP kinase, by both RET9 and RET51, appears to mediate the majority of RET-dependent resistance to chemotherapeutically induced apoptosis. MTC might be rendered more responsive to chemotherapeutic agents by the co-administration of a RET kinase inhibitor.

Original languageEnglish (US)
Pages (from-to)2019-2025
Number of pages7
JournalAnticancer Research
Volume28
Issue number4 B
StatePublished - Jul 1 2008

Keywords

  • Apoptosis
  • Doxorubicin
  • MAPK pathway
  • Medullary thyroid cancer
  • RET

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'RET activation inhibits doxorubicin-induced apoptosis in SK-N-MC cells'. Together they form a unique fingerprint.

  • Cite this

    Skinner, M. A., Lackey, K. E., & Freemerman, A. J. (2008). RET activation inhibits doxorubicin-induced apoptosis in SK-N-MC cells. Anticancer Research, 28(4 B), 2019-2025.