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Expression of TRAIL and TRAIL receptors in normal and malignant tissues

Cell Research 2005年第6期15卷 430-438页

作者： Raymond A DANIELS,Helen TURLEY,Fiona C KIMBERLEY,Juthathip MONGKOLSAPAYA,Paul CH’EN,Francesco PEZZELLA,Gavin R SCREATON Human Immunology Unit Weatherall Institute of Molecular Medicine University of Oxford John Radcliffe Hospital Oxford OX3 9DS UK Nuffield Department of Clinical Laboratory Sciences University of Oxford John Radcliffe Hospital Oxford OX3 9DS UK Hammersmith Hospital Du Cane Road London W12 0NN UK Hammersmith Hospital Du Cane Road London W12 0NN UK Human Immunology Unit Weatherall Institute of Molecular Medicine University of Oxford John Radcliffe Hospital Oxford OX3 9DS UK Nuffield Department of Clinical Laboratory Sciences University of Oxford John Radcliffe Hospital Oxford OX3 9DS UK Hammersmith Hospital Du Cane Road London W12 0NN UK

TRAIL, tumor necrosis factor-related apoptosis-inducing ligand, is a member of the TNF family of *** cells were initially found to have increased sensitivity to TRAIL compared with normal cells, raising hopes thatTRAIL would prove useful as an anti-tumor agent. The production of reliable monoclonal antibodies against TRAIL andits receptors that can stain fixed specimens will allow a thorough analysis of their expression on normal and malignanttissues. Here we report the generation of monoclonal antibodies against TRAIL and its four membrane-bound receptors(TR1–4), which have been used to stain a range of normal and malignant cells, as routinely fixed specimens. Low levelsof TRAIL expression were found to be limited mostly to smooth muscle in lung and spleen as well as glial cells in thecerebellum and follicular cells in the thyroid. Expression of the TRAIL decoy receptors (TR3 and 4) was not aswidespread as indicated by Northern blotting, suggesting that they may be less important for the control of TRAILcytotoxicity than previously thought. TR1 and TR2 expression increases significantly in a number of malignant tissues,but in some common malignancies their expression was low, or patchy, which may limit the therapeutic role of *** together, we have a panel of monoclonal antibodies that will allow a better assessment of the normal role ofTRAIL and allow assessment of biopsy material, possibly allowing the identification of tumors that may be amenable toTRAIL therapy.

关键词： apoptosis immunohistochemistry monoclonal antibodies tumor markers.

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