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Death receptor 6 (DR6) is a member of TNF receptor superfamily.DR6 is a typeⅠtransmembrane receptor, is 655 amino acids in length. Its molecular weight is about 35Kda. DR6 has a recognized signal peptide sequence (1～41 amino acids) in N terminal, DR6 has four extracellular cysteine region (42～211 amino acids). In its cytoplasm, DR6 contains a death domain (428～494 amino acids). DR6 is expressed highly in many organizations, especially the heart, brain, placenta, and immune lymphoid organs including the spleen, thymus, lymph nodes and bone marrow, and DR6 have been found in many cell lines are also highly expressed. DR6 can interact with TRADD and active both JNK and NF-κB. DR6 inhibits T, B cell proliferation and activation, and it also involved in inducing neurons cell apoptosis. Recently reported in the literature, APP is a DR6 ligand, can induce neuronal apoptosis. In order to study the role of DR6 in tumor cell line, we used the ligand of DR6-APP, purified APP, and we use APP to stimulate tumor cells to see its growth. At the same time, we transfected DR6 to tumor cell lines to see the cell growth. Using the principle of RNA interference, we obtain the DR6 knockdown cell lines and study the growth of the tumor cell lines. Result:(1) DR6 have a certain level of expression on different tumor cell lines; (2) Overexpression DR6 induced tumor cell apoptosis, after DR6 konckdown, the growth of tumor cell become slow; (3) DR6 can promote tumor cell growth through APP.
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