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K. Miyazaki, S. Saika, T. Miyamoto, Y. Ohnishi; Induction of Eyelid Tumor in XPC-/- Mice and TGFb-signal Transduction in Neoplastic Cells . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2441.
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Purpose: To assess TGF ß-signaling status in eyelid epidermal tumors of various differentiation levels, which have been induced by using 9,10-dimethyl-1,2-benzanthracene (DMBA) and Phorbol-12-myristate 13 acetate (TPA) in XPC-/- mice and wild type (WT) mice. Methods: Eight XPC-/- mice and two WT mice received topical administration of 50 ml of DMBA (0.2 mg/0.2 ml acetone) and TPA (20 nmol/200 ml acetone) in eyelid skin twice a week and were kept in a dark room up to 8 months. Paraffin sections of developed eyelid tumor were histologically examined and also immunostained for TGF ß receptor type II (TbRII), collagen IV, vimentin, Smad3, Erk-1 and BrdU. The findings were compared with those in the normal eyelid epidermal tissues.Results: All XPC-/- mice developed eyelid tumors within 3 months. Three-month treatment did not induce tumor lesion in WT mice. The KO mice were killed after 2-hr BrdU labeling. Histology included hyperplasia and benign papillomas of various differentiation stages. In well-differentiated papilloma, the basement membrane seems well formed and the expression of both Smad4 and TßRII was seen, but in poorly-differentiated papilloma expression of these molecules was less and immunoreactivity for Erk-1 and BrdU was positive in the nuclei of some of the neoplastic ells. In poorly-differentiated papillomas, the basement membrane was interrupted and vimentin was positive in neoplastic cells.Conclusions: Eyelid tumors could be induced in all the XPC-/- mice treated with topical DMBA and TPA. Immunohistochmeical data suggest cellular de-differentiation and the impairment of TGF ß signaling in the poorly-differentiated papilloma as compared with well-differentiated type.
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