Binding of B-cell maturation antigen to B-cell activating factor induces survival of multiple myeloma cells by activating Akt and JNK signaling pathways

Cell Biochem Funct. 2016 Mar;34(2):104-10. doi: 10.1002/cbf.3169. Epub 2016 Feb 24.

Abstract

B-cell maturation antigen (BCMA) is expressed on normal and malignant plasma cells and represents a potential target for therapeutic intervention. In this study, we characterized the mechanism underlying the protein kinase B (Akt) and c-Jun N-terminal kinase (JNK) pathways and BCMA interactions in regulating multiple myeloma (MM) cell survival. It was found that the expression levels of B cell-activating factor (BAFF) and BCMA were increased in MM cells as compared with those in normal controls. The proliferation of U266 cells was induced by recombinant human BAFF (rhBAFF) and could also be decreased by BCMA siRNA. The expression of Bcl-2 protein was up-regulated, and Bax protein was down-regulated after rhBAFF treatment, which could be reversed by BCMA siRNA. Similarly, the protein p-JNK and p-Akt were activated by rhBAFF and could be changed by BCMA siRNA. In addition, the BCMA mRNA and protein expression levels were decreased after treatment with Akt and JNK pathway inhibitors. These results suggest that Akt and JNK pathways are involved in the regulation of BCMA. A novel BAFF/BCMA signalling pathway in MM may be a new therapeutic target for MM.

Keywords: Akt signalling pathway; B cell-activating factor (BAFF); B-cell maturation antigen (BCMA); JNK signalling pathway; multiple myeloma (MM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • B-Cell Activating Factor / metabolism*
  • B-Cell Maturation Antigen / metabolism*
  • Binding Sites
  • Cell Survival
  • Female
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Male
  • Middle Aged
  • Multiple Myeloma / metabolism*
  • Multiple Myeloma / pathology*
  • Protein Binding
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction*
  • Tumor Cells, Cultured

Substances

  • B-Cell Activating Factor
  • B-Cell Maturation Antigen
  • Proto-Oncogene Proteins c-akt
  • JNK Mitogen-Activated Protein Kinases