Multiple myeloma cell killing by depletion of the MET receptor tyrosine kinase
Multiple myeloma cell killing by depletion of the MET receptor tyrosine kinase
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DOI：
10.1158/0008-5472.can-07-0770
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发表时间：
2007-10-15
期刊：
影响因子：
11.2
通讯作者：
Gandhi, Varsha
中科院分区：
文献类型：
--
作者：
Stellrecht, Christine M.;Phillip, Cornel J.;Gandhi, Varsha
Multiple myeloma (MM) is an invariably fatal plasma cell malignancy, primarily due to the therapeutic resistance which ultimately arises. Much of the resistance results from the expression of various survival factors. Despite this, the ribonucleoside analogue, 8-chloro-adenosine (8-Cl-Ado), is cytotoxic to a number of MM cell lines. Previously, we established that the analogue incorporates into the RNA and inhibits mRNA synthesis. Because 8-Cl-Ado is able to overcome survival signals present in MM cells and inhibits mRNA synthesis, it is likely that the drug induces cytotoxicity by depleting the expression of critical MM survival genes. We investigated this question using gene array analysis, real-time reverse transcription-PCR, and immunoblot analysis on 8-Cl-Ado-treated MM.lS cells and found that the mRNA and protein levels of the receptor tyrosine kinase MET decrease prior to apoptosis. To determine MET's role in 8-Cl-Ado cytotoxicity, we generated MM.lS clones stably expressing a MET ribozyme. None of the clones expressed
