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    Suppressor role of activating transcription factor 2 (ATF2) in skin cancer.

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    Authors
    Bhoumik, Anindita
    Fichtman, Boris
    Derossi, Charles
    Breitwieser, Wolfgang
    Kluger, Harriet M
    Davis, Sean
    Subtil, Antonio
    Meltzer, Paul
    Krajewski, Stan
    Jones, Nic
    Ronai, Ze'ev
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    Affiliation
    Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
    Issue Date
    2008-02-05
    
    Metadata
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    Abstract
    Activating transcription factor 2 (ATF2) regulates transcription in response to stress and growth factor stimuli. Here, we use a mouse model in which ATF2 was selectively deleted in keratinocytes. Crossing the conditionally expressed ATF2 mutant with K14-Cre mice (K14.ATF2(f/f)) resulted in selective expression of mutant ATF2 within the basal layer of the epidermis. When subjected to a two-stage skin carcinogenesis protocol [7,12-dimethylbenz[a]anthracene/phorbol 12-tetradecanoate 13-acetate (DMBA/TPA)], K14.ATF2(f/f) mice showed significant increases in both the incidence and prevalence of papilloma development compared with the WT ATF2 mice. Consistent with these findings, keratinocytes of K14.ATF2(f/f) mice exhibit greater anchorage-independent growth compared with ATF2 WT keratinocytes. Papillomas of K14.ATF2(f/f) mice exhibit reduced expression of presenilin1, which is associated with enhanced beta-catenin and cyclin D1, and reduced Notch1 expression. Significantly, a reduction of nuclear ATF2 and increased beta-catenin expression were seen in samples of squamous and basal cell carcinoma, as opposed to normal skin. Our data reveal that loss of ATF2 transcriptional activity serves to promote skin tumor formation, thereby indicating a suppressor activity of ATF2 in skin tumor formation.
    Citation
    Suppressor role of activating transcription factor 2 (ATF2) in skin cancer. 2008, 105 (5):1674-9 Proc. Natl. Acad. Sci. U.S.A.
    Journal
    Proceedings of the National Academy of Sciences of the United States of America
    URI
    http://hdl.handle.net/10541/58724
    DOI
    10.1073/pnas.0706057105
    PubMed ID
    18227516
    Type
    Article
    Language
    en
    ISSN
    1091-6490
    ae974a485f413a2113503eed53cd6c53
    10.1073/pnas.0706057105
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research
    Cell Regulation

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