Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-6 (IL-6), a pleiotropic cytokine with effects on several hematopoietic and other normal cells, is also important for the growth and survival of tumor cells such as murine plasmacytomas and human myelomas. Exploiting the 11A3 hybridoma cell line for its IL-6 requirement to proliferate in vitro, we used subtractive suppression hybridization (SSH) to identify genes whose expression is stimulated and/or repressed in response to IL-6. Northern blot analysis of 100 arbitrarily picked subtracted cDNA clones revealed that expression of 11 mRNAs were IL-6-modulated. Among these, eight were genes known to encode a variety of proteins such as enzymes (PCK, MTDNI), structural proteins (Tropoelastin), transcriptional regulators (BRG1) and proteins involved in cell division control (Cyclin A, OAZi) or cell signaling (PIX, TOPK/PBK). The recently identified MAPKK-like protein kinase TOPK/PBK gene represents a likely candidate IL-6 target gene as suggested by its significant up-regulated expression in hybridoma cells induced to grow by a brief IL-6 pulse. The diversity of growth-related genes identified in this study further emphasizes the central role of IL-6 in the regulation of myeloma cell expansion in addition to its previously demonstrated role in the inhibition of apoptosis.
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PMID:Regulation of growth-related genes by interleukin-6 in murine myeloma cells. 1245 69

[Figure: see text] Multiple myeloma (MM) remains an intractable hematological malignancy, despite recent advances in anti-MM drugs. Here, we show that role of PDZ binding kinase (PBK) in MM tumor growth. We identified that interleukin-6 (IL-6) readily increases PBK expression. Kaplan-Meier analysis showed that the MM patients with higher expression of PBK have a significant shorter survival time compared with those with moderate/lower expression of PBK. Knockout of PBK dramatically suppressed in vivo tumor growth in MM cells, while genome editing of PBK changing from asparagine to serine substitution (rs3779620) slightly suppresses the tumor formation. Mechanistically, loss of PBK increased the number of apoptotic cells with concomitant decrease in the phosphorylation level of Stat3 as well as caspase activities. A novel PBK inhibitor OTS514 significantly decreased KMS-11-derived tumor growth. These findings highlight the novel oncogenic role of PBK in tumor growth of myeloma, and it might be a novel therapeutic target for the treatment of patients with MM.
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PMID:Novel Interleukin-6 Inducible Gene PDZ-Binding Kinase Promotes Tumor Growth of Multiple Myeloma Cells. 3272 Dec 46