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

TACI 表达与人类骨髓瘤细胞系中成熟骨髓浆细胞特征和 C-MAF 过表达相关

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作者:Jérôme Moreaux, Dirk Hose, Michel Jourdan, Thierry Reme, Michael Hundemer, Marion Moos, Nicolas Robert, Philippe Moine, John De Vos, Hartmut Goldschmidt, Bernard Klein

Conclusions

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

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.

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