Over-expression of Ubiquitin C inhibits exacerbated chemically induced skin tumorigenesis in Pparβ/δ-null mice
Open Access
Author:
Kang, Satbyol
Area of Honors:
Biology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
Jeffrey Maurice Peters, Thesis Supervisor Dr. Bernhard Lüscher, Thesis Honors Advisor
Keywords:
Pparβ/δ chemoprevention Ubc skin tumorigenesis
Abstract:
Previous studies have shown that 12-O-tetradecanoylphorbol-13-acetate (TPA) induces expression of ubiquitin C (Ubc) in wild-type mouse skin but not in Pparβ/δ-null mice. Further, Pparβ/δ-null mice exhibit enhanced skin carcinogenesis due in part to decreased Ubc mediated degradation of PKCα. The present studies tested the hypothesis that increased expression of Ubc in Pparβ/δ-null mice could reverse the enhanced tumor formation in Pparβ/δ-null mice. A tetracycline inducible transgenic mouse model in which Ubc expression is driven by the keratin 5 promoter was generated and crossed with either wild-type or Pparβ/δ-null mice. Consistent with the previous studies, the onset of tumor formation was sooner, and Pparβ/δ-null mice exhibited increased tumor multiplicity and size compared to wild-type mice. While over-expression of Ubc had no effect on tumor onset or incidence in either wild-type or Pparβ/δ-null mice, it decreased tumor multiplicity and size in Pparβ/δ-null mice. These effects may be due to increased ubiquitin-dependent turnover of oncogenes. Results from these studies suggest that PPARβ/δ-dependent regulation of Ubc is important for PPARβ/δ-dependent chemoprevention in skin.
