The Polycomb group protein EZH2 is upregulated in proliferating, cultured human mantle cell lymphoma

Polycomb group (PcG) proteins are involved in the stable transmittance of t he repressive state of their gene targets throughout the cell cycle. Mis-ex pression of PcG proteins can lead to proliferative defects and tumorigenesi s. There are two separate multimeric PcG protein complexes: an EED-EZH2-con taining complex and a BMI1-RING1-containing complex. In the normal human fo llicle mantle, both PcG complexes have mutually exclusive expression patter ns. BMI1-RING1 is expressed, but EZH2-EED is not. Here, we studied the expr ession of both complexes in six cases of mantle cell lymphoma (MCL), which is derived from the follicle mantle. MCL cells can be cultured in vitro and stimulated to proliferation. We found that resting MCL cells expressed BMI 1-RING1, but not EZH2-EED, like normal mantle cells. Proliferating MCL cell s, however showed strongly enhanced expression of EZH2. Also, BMI1 and RING 1 continued to be expressed in proliferating MCL. This is the first demonst ration that EZH2 expression can be upregulated in fresh lymphoma cells, To test whether the enhanced EZH2 expression was causal for the increased prol iferation in MCL, we overexpressed EZH2 in two different cell lines. In the B cell-derived Ramos cell line, EZH2 overexpression caused an increase in the proliferation rate. This suggests a possible causal effect between EZH2 upregulation and increased proliferation in haematopoietic cells.