title: TACI expression is associated with a mature bone marrow plasma cell signature and C-MAF overexpression in human myeloma cell lines.
abstract: OBJECTIVE
  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
  
  
  CONCLUSIONS
  We conclude that TACI activation can upregulate c-maf expression which, in turn, controls cyclin D2, and integrin beta7 gene expression.
authors.affiliation: CHU Montpellier, Institute of Research in Biotherapy, Montpellier, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Moreaux
authors.forename: Dirk
authors.initials: D
authors.lastname: Hose
authors.forename: Michel
authors.initials: M
authors.lastname: Jourdan
authors.forename: Thierry
authors.initials: T
authors.lastname: Reme
authors.forename: Michael
authors.initials: M
authors.lastname: Hundemer
authors.forename: Marion
authors.initials: M
authors.lastname: Moos
authors.forename: Nicolas
authors.initials: N
authors.lastname: Robert
authors.forename: Philippe
authors.initials: P
authors.lastname: Moine
authors.forename: John
authors.initials: J
authors.lastname: De Vos
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
authors.forename: Bernard
authors.initials: B
authors.lastname: Klein
mesh_terms: D001853:Bone Marrow; D056742:Cyclin D2; D016213:Cyclins / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039641:Integrin beta Chains / Q000235:genetics; D009101:Multiple Myeloma / Q000473:pathology*; D010950:Plasma Cells / Q000166:cytology*; D051257:Proto-Oncogene Proteins c-maf / Q000235:genetics*; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C080336:CCND2 protein, human; D056742:Cyclin D2; D016213:Cyclins; D039641:Integrin beta Chains; C495607:MAF protein, human; D051257:Proto-Oncogene Proteins c-maf; C108467:TNFRSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; C091368:integrin beta7