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

2.50
Hdl Handle:
http://hdl.handle.net/10541/58724
Title:
Suppressor role of activating transcription factor 2 (ATF2) in skin cancer.
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
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.
Affiliation:
Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
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
Issue Date:
5-Feb-2008
URI:
http://hdl.handle.net/10541/58724
DOI:
10.1073/pnas.0706057105
PubMed ID:
18227516
Type:
Article
Language:
en
ISSN:
1091-6490
Appears in Collections:
All Paterson Institute for Cancer Research; Cell Regulation

Full metadata record

DC FieldValue Language
dc.contributor.authorBhoumik, Anindita-
dc.contributor.authorFichtman, Boris-
dc.contributor.authorDerossi, Charles-
dc.contributor.authorBreitwieser, Wolfgang-
dc.contributor.authorKluger, Harriet M-
dc.contributor.authorDavis, Sean-
dc.contributor.authorSubtil, Antonio-
dc.contributor.authorMeltzer, Paul-
dc.contributor.authorKrajewski, Stan-
dc.contributor.authorJones, Nic-
dc.contributor.authorRonai, Ze'ev-
dc.date.accessioned2009-04-01T23:28:46Z-
dc.date.available2009-04-01T23:28:46Z-
dc.date.issued2008-02-05-
dc.identifier.citationSuppressor role of activating transcription factor 2 (ATF2) in skin cancer. 2008, 105 (5):1674-9 Proc. Natl. Acad. Sci. U.S.A.en
dc.identifier.issn1091-6490-
dc.identifier.pmid18227516-
dc.identifier.doi10.1073/pnas.0706057105-
dc.identifier.urihttp://hdl.handle.net/10541/58724-
dc.description.abstractActivating 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.en
dc.language.isoenen
dc.subjectSkin Canceren
dc.subject.mesh9,10-Dimethyl-1,2-benzanthracene-
dc.subject.meshActivating Transcription Factor 2-
dc.subject.meshAnimals-
dc.subject.meshApoptosis-
dc.subject.meshCarcinogens-
dc.subject.meshCell Proliferation-
dc.subject.meshCyclin D1-
dc.subject.meshDNA-
dc.subject.meshEpidermis-
dc.subject.meshKeratinocytes-
dc.subject.meshMice-
dc.subject.meshMice, Knockout-
dc.subject.meshPapilloma-
dc.subject.meshPresenilin-1-
dc.subject.meshProto-Oncogene Proteins c-myb-
dc.subject.meshReceptor, Notch1-
dc.subject.meshSkin Neoplasms-
dc.subject.meshTetradecanoylphorbol Acetate-
dc.subject.meshTissue Array Analysis-
dc.subject.meshTumor Suppressor Proteins-
dc.subject.meshbeta Catenin-
dc.titleSuppressor role of activating transcription factor 2 (ATF2) in skin cancer.en
dc.typeArticleen
dc.contributor.departmentBurnham Institute for Medical Research, La Jolla, CA 92037, USA.en
dc.identifier.journalProceedings of the National Academy of Sciences of the United States of Americaen

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