Document Detail


Role for interleukin-6 and insulin-like growth factor-I via PI3-K/Akt pathway in the proliferation of CD56- and CD56+ multiple myeloma cells.
MedLine Citation:
PMID:  16728278     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: Several studies including ours have suggested that lack of CD56 in multiple myeloma (MM) defines a unique patient subset with poorer prognosis. However, the mechanism underlying this aggressive behavior of CD56(-) MM has not been well elucidated. Interleukin-6 (IL-6) or insulin-like growth factor I (IGF-I) induce proliferation of MM cells. In this study, we report about the relationship between CD56 expression and responsiveness to these cytokines. METHODS: We sorted out both CD56(-) and CD56(+) fractions from MM cell lines such as KMS-21-BM and U-266, and investigated their different responsiveness to IL-6 or IGF-I. Furthermore, we compared the effects of these cytokines on the regulation of cell-cycle distribution between CD56(-) and CD56(+) cells. RESULTS: Although CD56(-) cells in both KMS-21-BM and U-266 cells responded significantly to IL-6, CD56(+) cells did not. Ki-67(+) cells in the CD56(-) cells were significantly increased by IL-6. Western blotting showed that IL-6 phosphorylated Akt, and upregulated and downregulated the level of cyclin D1 and p27 protein in the CD56(-) KMS-21-BM cells, respectively. LY-294002 completely blocked these effects of IL-6. On the other hand, Ki-67(+) cells in the CD56(+) cells did not respond to IL-6. Anti-IGF-I mAb significantly reduced Ki-67(+) cells only in the CD56(+) cells. IGF-I phosphorylated Akt and upregulated cyclin D1 in the CD56(+) KMS-21-BM cells, which was completely blocked by LY294002. CONCLUSIONS: These results suggest that CD56(-) and CD56(+) MM cells could be stimulated by IL-6 and IGF-I, respectively, via PI3-K/Akt pathway, and provide useful information for anticytokine therapies.
Authors:
Naohi Sahara; Akihiro Takeshita; Takaaki Ono; Yuya Sugimoto; Miki Kobayashi; Kazuyuki Shigeno; Satoki Nakamura; Kaori Shinjo; Kensuke Naito; Kiyoshi Shibata; Takemi Otsuki; Hideharu Hayashi; Kazunori Ohnishi
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Experimental hematology     Volume:  34     ISSN:  0301-472X     ISO Abbreviation:  Exp. Hematol.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-05-26     Completed Date:  2006-07-18     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0402313     Medline TA:  Exp Hematol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  736-44     Citation Subset:  IM    
Affiliation:
Internal Medicine III, Hamamatsu University School of Medicine, Hamamatsu, Japan. sahara@hama-med.ac.jp
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / metabolism
Antibodies, Monoclonal / immunology,  pharmacology
Antigens, CD56*
Cell Cycle / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects*
Chromones / pharmacology
Cyclin D1 / metabolism
Enzyme Inhibitors
Gene Expression Regulation, Neoplastic / drug effects
Humans
Insulin-Like Growth Factor I / immunology,  metabolism,  pharmacology*
Interleukin-6 / immunology,  metabolism,  pharmacology*
Ki-67 Antigen
Morpholines / pharmacology
Multiple Myeloma / metabolism*
Oncogene Protein v-akt / metabolism
Phosphorylation
Protein Processing, Post-Translational / drug effects
Signal Transduction / drug effects*
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD56; 0/Chromones; 0/Enzyme Inhibitors; 0/Interleukin-6; 0/Ki-67 Antigen; 0/Morpholines; 136601-57-5/Cyclin D1; 154447-36-6/2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; 67763-96-6/Insulin-Like Growth Factor I; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Oncogene Protein v-akt

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