Inhibition of tumor growth and metastasis of human melanoma by intracellular anti-ATF-1 single chain Fv fragment

Didier Jean, Carmen Tellez, Suyun Huang, Darren W. Davis, Christiane J. Bruns, David J. McConkey, Steven H. Hinrichs, Menashe Bar-Eli

Research output: Contribution to journalArticlepeer-review

Abstract

Activating transcription factor-1 (ATF-1) and cAMP-responsive element (CRE)-binding protein (CREB) have been implicated in cAMP and Ca2+-induced transcriptional activation. The expression of the transcription factors CREB and ATF-1 is upregulated in metastatic melanoma cells. However, how overexpression of ATF-1/CREB contributes to the acquisition of the metastatic phenotype remains unclear. Here, the effect of disrupting ATF-1 activity was investigated using intracellular expression of an inhibitory anti-ATF-1 single chain antibody fragment (ScFv). Intracellular expression of ScFv anti-ATF-1 in MeWo melanoma cells caused significant reduction in CRE-dependent promoter activation. In addition, expression of ScFv anti-ATF-1 in melanoma cells suppressed their tumorigenicity and metastatic potential in nude mice. ScFv anti-ATF-1 rendered the melanoma cells susceptible to thapsigargin-induced apoptosis in vitro and caused massive apoptosis in tumors transplanted subcutaneously into nude mice, suggesting that ATF-1 and its associated proteins act as survival factor for human melanoma cells. This is the first report to demonstrate the potential of ScFv anti-ATF-1 as an inhibitor of tumor growth and metastasis of solid tumor in vivo.

Original languageEnglish (US)
Pages (from-to)2721-2730
Number of pages10
JournalOncogene
Volume19
Issue number22
DOIs
StatePublished - May 18 2000

Keywords

  • Apoptosis
  • Melanoma
  • Metastasis
  • Transcriptional regulation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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