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- Title
Inhibition of tumor growth and metastasis of human melanoma by intracellular anti-ATF-1 single chain Fv fragment.
- Authors
Jean, Didier; Tellez, Carmen; Huang, Suyun; Davis, Darren W; Bruns, Christiane J; McConkey, David J; Hinrichs, Steven H; Bar-Eli, Menashe
- 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. Oncogene (2000) 19, 2721–2730
- Subjects
MELANOMA; METASTASIS; APOPTOSIS; TUMOR growth
- Publication
Oncogene, 2000, Vol 19, Issue 22, p2721
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1203569