An ATF2-derived peptide sensitizes melanomas to apoptosis and inhibits their growth and metastasis.
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.
Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York 10029, USA.
Anindita
A
Bhoumik
Tian-Gui
TG
Huang
Vladimir
V
Ivanov
Lisa
L
Gangi
Rui F
RF
Qiao
Savio L C
SL
Woo
Shu-Hsia
SH
Chen
Ze'ev
Z
Ronai
D051698:Activating Transcription Factor 2; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D002469:Cell Separation; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008024:Ligands; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D010455:Peptides / Q000737:chemistry*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D051698:Activating Transcription Factor 2; C497106:Atf2 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D008024:Ligands; D010455:Peptides; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D012313:RNA