RGD Reference Report - Constitutive activation and targeted disruption of signal transducer and activator of transcription 3 (Stat3) in mouse epidermis reveal its critical role in UVB-induced skin carcinogenesis. - Rat Genome Database

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Constitutive activation and targeted disruption of signal transducer and activator of transcription 3 (Stat3) in mouse epidermis reveal its critical role in UVB-induced skin carcinogenesis.

Authors: Kim, DJ  Angel, JM  Sano, S  DiGiovanni, J 
Citation: Kim DJ, etal., Oncogene. 2009 Feb 19;28(7):950-60. doi: 10.1038/onc.2008.453. Epub 2009 Jan 12.
RGD ID: 8694289
Pubmed: PMID:19137019   (View Abstract at PubMed)
PMCID: PMC2645481   (View Article at PubMed Central)
DOI: DOI:10.1038/onc.2008.453   (Journal Full-text)

In this study, the potential role of Stat3 in UVB-induced skin carcinogenesis was examined using skin-specific gain and loss of function transgenic mice, that is, K5.Stat3C and K5Cre.Stat3(fl/fl) mice, respectively. The epidermis of Stat3-deficient mice was highly sensitive to UVB-induced apoptosis, whereas the epidermis of K5.Stat3C mice was more resistant to UVB-induced apoptosis. In particular, the status of Stat3 influenced the survival of ultraviolet-photoproduct cells, including those located in the hair follicles. K5.Stat3C mice exhibited significantly increased epidermal proliferation and hyperplasia in response to UVB irradiation, whereas Stat3-deficient mice showed reduced epidermal proliferation and hyperplasia. Expression of target genes regulated by Stat3, such as cyclin D1 and Bcl-x(L), was increased in epidermis of both control and UVB-irradiated K5.Stat3C mice, and downregulated in epidermis of both control and UVB-irradiated K5Cre.Stat3(fl/fl) mice. Following UVB irradiation, the formation of skin tumors in K5.Stat3C mice was accelerated and both the incidence and multiplicity of skin tumors were significantly greater than wild-type controls. In contrast, Stat3-deficient mice were resistant to UVB skin carcinogenesis. These results show that Stat3 plays an important role in the development of UVB-induced skin tumors through its effects on both survival and proliferation of keratinocytes during carcinogenesis.




  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
STAT3HumanSkin Neoplasms  ISOStat3 (Mus musculus) RGD 
Stat3RatSkin Neoplasms  ISOStat3 (Mus musculus) RGD 
Stat3MouseSkin Neoplasms  IMP  RGD 


Genes (Rattus norvegicus)
Stat3  (signal transducer and activator of transcription 3)

Genes (Mus musculus)
Stat3  (signal transducer and activator of transcription 3)

Genes (Homo sapiens)
STAT3  (signal transducer and activator of transcription 3)