Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Leukemia. 2012 May;26(5):1073-80. doi: 10.1038/leu.2011.263. Epub 2011 Sep 23.
Bone morphogenetic proteins (BMPs) have been shown to induce apoptosis and growth arrest in myeloma cells. However, the molecular mechanisms behind these events are not known. The MYC oncogene is a master regulator of cell growth and protein synthesis and MYC overexpression has been proposed to be associated with the progression of multiple myeloma. Here, we show that BMP-induced apoptosis in myeloma cells is dependent on downregulation of MYC. Moreover, the results suggest that targeting the MYC addiction in multiple myeloma is an efficient way of killing a majority of primary myeloma clones. We also found that myeloma cells harboring immunoglobulin (IG)-MYC translocations evaded BMP-induced apoptosis, suggesting a novel way for myeloma cells to overcome potential tumor suppression by BMPs.
骨形态发生蛋白（BMPs）已被证明可诱导骨髓瘤细胞凋亡和生长停滞。然而，这些事件背后的分子机制尚不清楚。MYC 癌基因是细胞生长和蛋白质合成的主要调节因子，MYC 过表达被认为与多发性骨髓瘤的进展有关。在这里，我们表明骨髓瘤细胞中的 BMP 诱导的凋亡依赖于 MYC 的下调。此外，结果表明，针对多发性骨髓瘤中的 MYC 成瘾是杀死大多数原发性骨髓瘤克隆的有效方法。我们还发现携带免疫球蛋白（IG）-MYC 易位的骨髓瘤细胞逃避了 BMP 诱导的凋亡，这表明骨髓瘤细胞克服 BMP 潜在肿瘤抑制作用的一种新方法。
