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Deletion of Prostaglandin E2 EP2 Receptor Protects against Ultraviolet-Induced Carcinogenesis, but Increases Tumor Aggressiveness  Sabine Brouxhon, Raymond.

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Presentation on theme: "Deletion of Prostaglandin E2 EP2 Receptor Protects against Ultraviolet-Induced Carcinogenesis, but Increases Tumor Aggressiveness  Sabine Brouxhon, Raymond."— Presentation transcript:

1 Deletion of Prostaglandin E2 EP2 Receptor Protects against Ultraviolet-Induced Carcinogenesis, but Increases Tumor Aggressiveness  Sabine Brouxhon, Raymond L. Konger, JoAnne VanBuskirk, Tzong-jen Sheu, Julie Ryan, Brandon Erdle, Anthony Almudevar, Richard M. Breyer, Glynis Scott, Alice P. Pentland  Journal of Investigative Dermatology  Volume 127, Issue 2, Pages (February 2007) DOI: /sj.jid Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions

2 Figure 1 Modest UVR exposure does not stimulate proliferation in EP2−/− mice. Proliferation present in the epithelium of WT, EP2+/−, and EP2−/− animals was determined 72hours post UV-irradiation. Animals were exposed to either no light (control), or to 180mJ/cm2 UVR. UV-induced proliferation in WT animals is significantly different from that in EP2−/−, P<0.05, Students t-test. Data are expressed as the mean±SEM. N=4. Journal of Investigative Dermatology  , DOI: ( /sj.jid ) Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions

3 Figure 2 EP2 deletion protects against UV-induced tumors. Mice were photographed after completion of the 30-week UV-irradiation protocol. (a) Total tumors per mouse were tracked weekly for 15 weeks after cessation of UVR. Using a Mann–Whitney test, a statistically significant difference was seen between the WT and the EP2+/− and WT or EP2+/− mice (P<0.01). No statistically significant difference was evident between the WT and the EP2+/− genotype (N=10), EP2+/− (N=9) and EP2−/− (N=10). Data are expressed as the mean +/− SEM. (b) Progressive tumor incidence in WT, EP2+/−, and EP2+/− mice. No significant differences were observed. (c) Representative tumors on UVR exposed mice of each genotype. Journal of Investigative Dermatology  , DOI: ( /sj.jid ) Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions

4 Figure 3 MMP-2 and MMP-9 activity is increased in epidermal extracts of EP2−/− animals. UVR produces net increases in the activities of MMP-2 and MMP-9 in EP2−/− animals compared to WT animals 24hours after UV exposure. Activity returns to baseline 72hours post UVR. Data are expressed as the mean±SEM in a representative experiment. N=2. Journal of Investigative Dermatology  , DOI: ( /sj.jid ) Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions

5 Figure 4 UVR-induction of MMP-2 and MMP-9 is increased in EP2−/− animals compared to WT controls. Snap-frozen epidermal extracts from control and UV-exposed WT and EP2−/− animals were studied at baseline and 24hours after UV exposure as described in Materials and Methods. A representative zymogram is shown. N=4. Journal of Investigative Dermatology  , DOI: ( /sj.jid ) Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions


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