PMID- 24509533
OWN - NLM
STAT- MEDLINE
DCOM- 20140819
LR  - 20211021
IS  - 1523-1747 (Electronic)
IS  - 0022-202X (Linking)
VI  - 134
IP  - 7
DP  - 2014 Jul
TI  - The oncogene ATF3 is potentiated by cyclosporine A and ultraviolet light A.
PG  - 1998-2004
LID - S0022-202X(15)36904-9 [pii]
LID - 10.1038/jid.2014.77 [doi]
AB  - Cutaneous squamous cell carcinoma (SCC) represents the most important cutaneous 
      complication following organ transplantation. It develops mostly on sun-exposed 
      areas. A recent study showed the role of activating transcription factor 3 (ATF3) 
      in SCC development following treatment with calcineurin inhibitors. It has been 
      reported that ATF3, which may act as an oncogene, is under negative 
      calcineurin/nuclear factor of activated T cells (NFAT) control and is upregulated 
      by calcineurin inhibitors. Still, these findings do not fully explain the 
      preferential appearance of SCC on chronically sun-damaged skin. We analyzed the 
      influence of UV radiation on ATF3 expression and its potential role in SCC 
      development. We found that ATF3 is a specifically induced AP1 member in SCC of 
      transplanted patients. Its expression was strongly potentiated by combination of 
      cyclosporine A and UVA treatment. UVA induced ATF3 expression through reactive 
      oxygen species-mediated nuclear factor erythroid 2-related factor 2 (NRF2) 
      activation independently of calcineurin/NFAT inhibition. Activated NRF2 directly 
      binds to ATF3 promoter, thus inducing its expression. These results demonstrate 
      two mechanisms that independently induce and, when combined together, potentiate 
      the expression of ATF3, which may then force SCC development. Taking into account 
      the previously defined role of ATF3 in the SCC development, these findings may 
      provide an explanation and a mechanism for the frequently observed burden on SCCs 
      on sun-exposed areas of the skin in organ transplant recipients treated by 
      calcineurin inhibitors.
FAU - Dziunycz, Piotr J
AU  - Dziunycz PJ
AD  - Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. 
      Electronic address: piotr.dziunycz@usz.ch.
FAU - Lefort, Karine
AU  - Lefort K
AD  - Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
FAU - Wu, Xunwei
AU  - Wu X
AD  - Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard 
      University, Charlestown, Massachusetts, USA.
FAU - Freiberger, Sandra N
AU  - Freiberger SN
AD  - Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
FAU - Neu, Johannes
AU  - Neu J
AD  - Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
FAU - Djerbi, Nadia
AU  - Djerbi N
AD  - Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
FAU - Iotzowa-Weiss, Guergana
AU  - Iotzowa-Weiss G
AD  - Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
FAU - French, Lars E
AU  - French LE
AD  - Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
FAU - Dotto, Gian-Paolo
AU  - Dotto GP
AD  - Department of Biochemistry, University of Lausanne, Epalinges, Switzerland; 
      Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard 
      University, Charlestown, Massachusetts, USA.
FAU - Hofbauer, Gunther F L
AU  - Hofbauer GFL
AD  - Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
LA  - eng
PT  - Journal Article
DEP - 20140207
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (ATF3 protein, human)
RN  - 0 (Activating Transcription Factor 3)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (Reactive Oxygen Species)
RN  - 83HN0GTJ6D (Cyclosporine)
SB  - IM
CIN - J Dtsch Dermatol Ges. 2014 Sep;12(9):833. PMID: 25176466
MH  - Activating Transcription Factor 3/*genetics
MH  - Carcinoma, Squamous Cell/etiology/*genetics/pathology
MH  - Cyclosporine/*pharmacology
MH  - Humans
MH  - Immunosuppressive Agents/pharmacology
MH  - Keratinocytes/cytology/physiology/radiation effects
MH  - NF-E2-Related Factor 2/metabolism
MH  - Neoplasms, Radiation-Induced/*genetics/pathology
MH  - Organ Culture Techniques
MH  - Organ Transplantation/adverse effects
MH  - Primary Cell Culture
MH  - Reactive Oxygen Species/metabolism
MH  - Skin/pathology/radiation effects
MH  - Skin Neoplasms/etiology/*genetics/pathology
MH  - Tumor Cells, Cultured
MH  - Ultraviolet Rays/*adverse effects
EDAT- 2014/02/11 06:00
MHDA- 2014/08/20 06:00
CRDT- 2014/02/11 06:00
PHST- 2013/10/11 00:00 [received]
PHST- 2013/12/23 00:00 [revised]
PHST- 2014/01/21 00:00 [accepted]
PHST- 2014/02/11 06:00 [entrez]
PHST- 2014/02/11 06:00 [pubmed]
PHST- 2014/08/20 06:00 [medline]
AID - S0022-202X(15)36904-9 [pii]
AID - 10.1038/jid.2014.77 [doi]
PST - ppublish
SO  - J Invest Dermatol. 2014 Jul;134(7):1998-2004. doi: 10.1038/jid.2014.77. Epub 2014 
      Feb 7.