骨髓微环境对多发性骨髓瘤瘤细胞AP-1家族成员基因表达的调节作用

本研究旨在探讨骨髓微环境对多发性骨髓瘤(MM)细胞AP-1家族成员基因的调节作用。采用免疫磁珠方法分选8例多发性骨髓瘤患者CD138+的瘤细胞并与破骨细胞共培养,用实时定量PCR方法检测与破骨细胞共培养的瘤细胞和与破骨细胞共培养的瘤细胞AP-1家族成员c-jun、junD、fos和fosB的表达量。结果显示,多发性骨髓瘤患者的外周血单个核细胞经破骨细胞培养液培养后10-14天形成破骨细胞,瘤细胞与破骨细胞共培养后与未与破骨细胞共培养相比较,细胞活力明显增高,c-jun、junD、fos和fosB表达量均降低。结论:骨髓微环境可抑制AP-1家族成员的表达,促进MM瘤细胞存活,抑制瘤细胞凋亡。

Role of Bone Marrow Microenvironment in Regulation of AP-1 Gene Expression in Multiple Myeloma Cells

This study was aimed to investigate the role of bone marrow microenvironment in the regulation of activator protein 1 （ AP-1 ） expression in multiple myeloma （MM） cells. The primary myeloma cells （ CD138＋ cells） from 8 patients with MM were sorted by using immunomagnetic beads and were cocultured with osteoclasts in α-MEM supplemented with 10% fetal bovine serum, antibotics, RNAKL （50 ng/ml） and macrophage colony-stimulating factor （25 ng/ml） for 10 to 14 days at 2.5 ×10^6 cells/ml. The expression levels of genes c-jun, junD los and fosB were detected by real-time PCR. The results showed that the osteoclasts were observed after coculture of manonuclear cells in peripheral blood of MM patients with osteoclasts for 10 - 14 days. As compared with control （ without coculture with osteoclasts）, the viability of MM cells cocultured with osteoclasts obriously increased, the expression levels of c-jun, junD, los and fosB decreased to 25, 7% - 1.66%, 68.49% - 8.54%, 10.35% - 0.19% and 36.63% - 3.44% of the control respectively. It is concluded that the bone marrow microenvironment can inhibit the expression of c-jun, junD, fos and fosB promote myeloma cell proliferation and maintain cell survival.