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K Miyazaki, S Saika, Y Okada, Y Ohnishi; Induction of Eyelid Tumor in XPC Knockout Mice and TGFß-signal Transduction in Neoplastic Cells . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3036.
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Purpose:To investigate whether it was possible to induce a neoplasm using 9,10-dimethyl-1,2-benzanthracene (DMBA) eye drops in XPC-/-mice and also to assess TGFß-signal transduction in the developing tumor. Methods:Two XPC-/- mice received a 50 µL of DMBA (0.2 µg/0.2 ml acetone) eye drops once weekly in a dark room. Sixteen week later, one animal developed an eyelid tumor. The animal was killed after 2-hr BrdU labeling at Week 18. Paraffin sections of the tumor were immunostained for TGFß receptor type II (TGFßRII), Smad3, Erk-1 and BrdU. The findings were compared with those in the normal tissues. Results:Light microscopic histology showed that the tumor was papilloma, which was considered to be benign. The expressions of TGFßRII and Smad3 were much less in the neoplastic cells as compared with cells of normal tissue. No difference was observed between subcellular location of Erk-1 or BrdU uptake by the neoplastic cells and cells of healthy tissue. Conclusion:A benign epithelial neoplasm could be induced in the eyelid of an XPC-/- mouse using DMBA eye drops. Reduced expression of TGFßRII and Smad3 suggested impairment of TGFß signal transduction. Normal-like tumor cell proliferation and MAP kinase status in the developed tumor might also support the histological diagnosis of benign epithelial neoplasm.
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