PMID- 18227516
OWN - NLM
STAT- MEDLINE
DCOM- 20080307
LR  - 20240316
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 105
IP  - 5
DP  - 2008 Feb 5
TI  - Suppressor role of activating transcription factor 2 (ATF2) in skin cancer.
PG  - 1674-9
LID - 10.1073/pnas.0706057105 [doi]
AB  - 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.
FAU - Bhoumik, Anindita
AU  - Bhoumik A
AD  - Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
FAU - Fichtman, Boris
AU  - Fichtman B
FAU - Derossi, Charles
AU  - Derossi C
FAU - Breitwieser, Wolfgang
AU  - Breitwieser W
FAU - Kluger, Harriet M
AU  - Kluger HM
FAU - Davis, Sean
AU  - Davis S
FAU - Subtil, Antonio
AU  - Subtil A
FAU - Meltzer, Paul
AU  - Meltzer P
FAU - Krajewski, Stan
AU  - Krajewski S
FAU - Jones, Nic
AU  - Jones N
FAU - Ronai, Ze'ev
AU  - Ronai Z
LA  - eng
SI  - GEO/GSE9328
GR  - 12485/CRUK_/Cancer Research UK/United Kingdom
GR  - R01 CA099961/CA/NCI NIH HHS/United States
GR  - CA099961/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080128
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Activating Transcription Factor 2)
RN  - 0 (Carcinogens)
RN  - 0 (Notch1 protein, mouse)
RN  - 0 (Presenilin-1)
RN  - 0 (Proto-Oncogene Proteins c-myb)
RN  - 0 (Receptor, Notch1)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (beta Catenin)
RN  - 136601-57-5 (Cyclin D1)
RN  - 57-97-6 (9,10-Dimethyl-1,2-benzanthracene)
RN  - 9007-49-2 (DNA)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - 9,10-Dimethyl-1,2-benzanthracene/toxicity
MH  - Activating Transcription Factor 2/analysis/genetics/*physiology
MH  - Animals
MH  - Apoptosis
MH  - Carcinogens/toxicity
MH  - Cell Proliferation
MH  - Cyclin D1/metabolism
MH  - DNA/biosynthesis
MH  - Epidermis/drug effects/metabolism/pathology
MH  - Keratinocytes/drug effects/metabolism/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - Papilloma/chemically induced/*genetics/pathology
MH  - Presenilin-1/metabolism
MH  - Proto-Oncogene Proteins c-myb/metabolism
MH  - Receptor, Notch1/metabolism
MH  - Skin Neoplasms/chemically induced/*genetics/pathology
MH  - Tetradecanoylphorbol Acetate/toxicity
MH  - Tissue Array Analysis
MH  - Tumor Suppressor Proteins/analysis/genetics/*physiology
MH  - beta Catenin/metabolism
PMC - PMC2234203
COIS- The authors declare no conflict of interest.
EDAT- 2008/01/30 09:00
MHDA- 2008/03/08 09:00
PMCR- 2008/08/05
CRDT- 2008/01/30 09:00
PHST- 2008/01/30 09:00 [pubmed]
PHST- 2008/03/08 09:00 [medline]
PHST- 2008/01/30 09:00 [entrez]
PHST- 2008/08/05 00:00 [pmc-release]
AID - 0706057105 [pii]
AID - 8914 [pii]
AID - 10.1073/pnas.0706057105 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1674-9. doi: 10.1073/pnas.0706057105. 
      Epub 2008 Jan 28.