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J Clin Invest. 2002 Sep;110(5):643-50.

An ATF2-derived peptide sensitizes melanomas to apoptosis and inhibits their growth and metastasis.

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  • 1Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York 10029, USA.

Abstract

Melanomas are among the aggressive tumor types because of their notorious resistance to treatment and their high capacity to metastasize. ATF2 is among transcription factors implicated in the progression of melanoma and its resistance to treatment. Here we demonstrate that the expression of a peptide spanning amino acids 50-100 of ATF2 (ATF2(50-100)) reduces ATF2 transcriptional activities while increasing the expression and activity of c-Jun. Altering the balance of Jun/ATF2 transcriptional activities sensitized melanoma cells to apoptosis, an effect that could be attenuated by inhibiting c-Jun. Inhibition of ATF2 via RNA interference likewise increased c-Jun expression and primed melanoma cells to undergo apoptosis. Growth and metastasis of SW1 and B16F10 mouse melanomas were inhibited by ATF2(50-100) to varying degrees up to a complete regression, depending on the mode (inducible, constitutive, or adenoviral delivery) of its expression.

PMID:
12208865
[PubMed - indexed for MEDLINE]
PMCID:
PMC151112
Free PMC Article
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