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Cell Rep. 2016 May 31;15(9):1884-92. doi: 10.1016/j.celrep.2016.04.072. Epub 2016 May 19.

A Transcriptionally Inactive ATF2 Variant Drives Melanomagenesis.

Author information

1
Tumor Initiation and Maintenance Program, Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
2
Division of Cancer Epidemiology and Genetics, Laboratory of Translational Genomics, National Cancer Institute, Bethesda, MD 20892, USA.
3
Department of Dermatology, University of Zürich, University of Zürich Hospital, Zürich 8091, Switzerland.
4
Oncogenomics Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.
5
Departments of Dermatology and Pathology, Yale University School of Medicine, New Haven, CT 06520, USA.
6
Tumor Initiation and Maintenance Program, Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. Electronic address: zeev@ronailab.net.

Abstract

Melanoma is one of the most lethal cutaneous malignancies, characterized by chemoresistance and a striking propensity to metastasize. The transcription factor ATF2 elicits oncogenic activities in melanoma, and its inhibition attenuates melanoma development. Here, we show that expression of a transcriptionally inactive form of Atf2 (Atf2(Δ8,9)) promotes development of melanoma in mouse models. Atf2(Δ8,9)-driven tumors show enhanced pigmentation, immune infiltration, and metastatic propensity. Similar to mouse Atf2(Δ8,9), we have identified a transcriptionally inactive human ATF2 splice variant 5 (ATF2(SV5)) that enhances the growth and migration capacity of cultured melanoma cells and immortalized melanocytes. ATF2(SV5) expression is elevated in human melanoma specimens and is associated with poor prognosis. These findings point to an oncogenic function for ATF2 in melanoma development that appears to be independent of its transcriptional activity.

PMID:
27210757
PMCID:
PMC4889472
DOI:
10.1016/j.celrep.2016.04.072
[Indexed for MEDLINE]
Free PMC Article

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