Skin cancers are the most common cancers in the United States. Exposure to UVB radiation is a major risk factor for skin cancer induction. SCF beta-TrCP E3 ubiquitin ligase has been found to be involved in cell cycle, cell proliferation and transformation. Aberrant up-regulation of beta-transducin repeats-containing proteins (beta-TrCP) is often found in cancer cell lines and primary tumors. We have previously demonstrated that beta-TrCP2 is over-expressed in chemically induced mouse skin tumors [1]. Various cellular stress stimuli, including UVB, induce an increase in beta-TrCP1 mRNA and protein levels in human cells [2]. We have previously shown that inhibition of beta-TrCP function, by induction of dominant negative beta-TrCP2 (beta-TrCP2(Delta F)), in vitro in hTERT immortalized normal keratinocytes, results in increase in UVB induced apoptosis [3]. We have generated transgenic mice with inducible, selective expression of dominant negative beta-TrCP2 in epidermis with the Keratin 5 promoter (K5-rTA x TRE-HA-beta-TrCP Delta F). Here we report that inhibition of beta-TrCP function in mouse epidermis results in decrease in UVB-induced edema, hyperplasia, and inflammatory response and increment in UVB-induced apoptosis in skin. Our results suggest that beta-TrCP may be an essential player in UVB induced responses in skin and can be a potential therapeutic target for skin cancer. Published by Elsevier Inc.
机构:
Univ Wurzburg, Med Ctr, Div Hematol & Oncol, Dept Internal Med 2, D-97070 Wurzburg, GermanyUniv Wurzburg, Med Ctr, Div Hematol & Oncol, Dept Internal Med 2, D-97070 Wurzburg, Germany
Bommert, Kurt
;
Bargou, Ralf C.
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Univ Wurzburg, Med Ctr, Div Hematol & Oncol, Dept Internal Med 2, D-97070 Wurzburg, GermanyUniv Wurzburg, Med Ctr, Div Hematol & Oncol, Dept Internal Med 2, D-97070 Wurzburg, Germany
Bargou, Ralf C.
;
Stuehmer, Thorsten
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Univ Wurzburg, Med Ctr, Div Hematol & Oncol, Dept Internal Med 2, D-97070 Wurzburg, GermanyUniv Wurzburg, Med Ctr, Div Hematol & Oncol, Dept Internal Med 2, D-97070 Wurzburg, Germany
机构:
Univ Wurzburg, Med Ctr, Div Hematol & Oncol, Dept Internal Med 2, D-97070 Wurzburg, GermanyUniv Wurzburg, Med Ctr, Div Hematol & Oncol, Dept Internal Med 2, D-97070 Wurzburg, Germany
Bommert, Kurt
;
Bargou, Ralf C.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Wurzburg, Med Ctr, Div Hematol & Oncol, Dept Internal Med 2, D-97070 Wurzburg, GermanyUniv Wurzburg, Med Ctr, Div Hematol & Oncol, Dept Internal Med 2, D-97070 Wurzburg, Germany
Bargou, Ralf C.
;
Stuehmer, Thorsten
论文数: 0引用数: 0
h-index: 0
机构:
Univ Wurzburg, Med Ctr, Div Hematol & Oncol, Dept Internal Med 2, D-97070 Wurzburg, GermanyUniv Wurzburg, Med Ctr, Div Hematol & Oncol, Dept Internal Med 2, D-97070 Wurzburg, Germany