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Title 

Roles of protein phosphatase 1 and 2A in an IL-6-mediated autocrine growth loop of human myeloma cells

Authors 

Hyung Sik KangBok Soo LeeYoung YangChong Won ParkHyun Jung HaKwang Ho PyunIn Pyo Choi

Publisher 

Elsevier

Issue Date 

1996

Citation 

Cellular Immunology, vol. 168, no. 2, pp. 174-183

Keywords 

glycoprotein gp 130interleukin 6n (6 aminohexyl) 5 chloro 1 naphthalenesulfonamidephosphoprotein phosphatasecell proliferationhumanhuman cellmultiple myelomamyeloma celltumor cells

Abstract 

Deregulation of IL-6 production is one of the major causes for human multiple myeloma. Exogenous IL-6 stimulated the proliferation of fresh human myeloma cells and the myeloma cell line, U266, which produced IL-6 spontaneously. Anti-IL-6 antibody and IL-6 antisense oligonucleotide suppressed the IL-8-stimulated myeloma cell proliferation, indicating that IL-6 induced the myeloma cell proliferation via an autocrine loop. Okadaic acid, an inhibitor of protein phosphatase 1 and 2A, inhibited the U266 cell proliferation at a concentration of less than 1 ng/ml. At this concentration, okadaic acid suppressed the IL-6-induced IL-6 gene expression of myeloma cells. It seems that the okadaic acid blocked the myeloma cell proliferation by reducing IL-6 synthesis in myeloma cells. In addition, IL-6 itself also regulated IL-6 receptor expression. Analysis by FACScan and RT-PCR showed that anti-PL-6 antibody treatment up-regulated IL-6 receptor expression. Interestingly, the presence of okadaic acid induced the up-regulation of IL-6 receptor expression as well as the down-regulation of IL-6-induced gp130 phosphorylation in the myeloma cells. Taken together, these data suggest that protein phosphatase 1 and 2A are involved in IL-6-mediated autocrine growth of human myeloma cells by modulating IL-6 signaling and IL-6 receptor expression in myeloma cells.

ISSN 

0008-8749

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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