TACI expression is associated with a mature bone marrow plasma cell signature and C-MAF overexpression in human myeloma cell lines

Haematologica. 2007 Jun;92(6):803-11. doi: 10.3324/haematol.10574.

Abstract

Background and objectives: BAFF and APRIL stimulate the growth of multiple myeloma (MM) cells. BAFF and APRIL share two receptors--TACI and BCMA--and BAFF binds to a third receptor, BAFF-R. We previously reported that TACI gene expression is bimodal in 18 human MM cell lines (HMCL), being either present or absent, unlike BCMA that is expressed on all HMCL. BAFF-R is lacking. TACI expression is a good indicator of a BAFF-binding receptor in HMCL. In primary MM cells, the level of TACI expression correlates with a characteristic phenotypic pattern: TACIhighMM cells resemble bone marrow plasma cells and TACIlow resemble plasmablasts. The aim of this study was to further characterize the role of TACI expression in MM DESIGN AND METHODS: Using gene expression profiling, we investigated whether these patterns are kept in TACI+ or TACI- HMCL.

Results: Eighty genes/EST interrogated by Affymetrix microarrays were differentially expressed between TACI+ and TACI- HMCL, particularly c-maf, cyclin D2, and integrin beta7. Triggered by the finding that TACI and c-maf expressions correlate in TACI+ HMCL, we demonstrated that TACI activation influences c-maf expression: (i) activation of TACI by BAFF or APRIL increases c-maf, cyclin D2, and integrin beta7 gene expressions in TACI+ HMCL, (ii) blocking of autocrine BAFF/APRIL stimulation in some TACI+ HMCL by the TACI-Fc fusion protein reduces c-maf, cyclin D2, and integrin beta7 gene expression, (iii) nucleofection of siRNA to c-maf decreases c-maf mRNA levels and reduces the expression of cyclin D2 and integrin beta7 gene expressions, without affecting TACI expression

Interpretation and conclusions: We conclude that TACI activation can upregulate c-maf expression which, in turn, controls cyclin D2, and integrin beta7 gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow
  • Cyclin D2
  • Cyclins / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Integrin beta Chains / genetics
  • Multiple Myeloma / pathology*
  • Plasma Cells / cytology*
  • Proto-Oncogene Proteins c-maf / genetics*
  • Transmembrane Activator and CAML Interactor Protein / genetics
  • Transmembrane Activator and CAML Interactor Protein / metabolism*

Substances

  • CCND2 protein, human
  • Cyclin D2
  • Cyclins
  • Integrin beta Chains
  • MAF protein, human
  • Proto-Oncogene Proteins c-maf
  • TNFRSF13B protein, human
  • Transmembrane Activator and CAML Interactor Protein
  • integrin beta7