Mortenson Melinda M, Schlieman Michael G, Virudachalam Subbulakshmi, Lara Primo N, Gandara David G, Davies Angela M, Bold Richard J
Division of Surgical Oncology, Suite 3010, University of California, Davis Cancer Center, 4501 X Street, Sacramento, CA 95817, USA.
Lung Cancer. 2005 Aug;49(2):163-70. doi: 10.1016/j.lungcan.2005.01.006.
Overexpression of the anti-apoptotic protein BCL-2 is frequently observed in small cell lung cancers (SCLC) and is associated with chemoresistance. We examined the signaling pathways involved in upregulation of BCL-2 in SCLC, and whether inhibition of NF-kappaB using the 26S proteasome inhibitor bortezomib had any effect on BCL-2 levels or apoptosis. Mutation of a NF-kappaB site in the BCL-2 promoter reduced promoter activity to less than 20% of the wild-type promoter. Treatment with bortezomib resulted in decreased transcription of the BCL-2 promoter, decreased BCL-2 levels, and induced apoptosis. These data provide the necessary laboratory background for further investigation of bortezomib in the treatment of SCLC.
抗凋亡蛋白BCL-2的过表达在小细胞肺癌（SCLC）中经常被观察到，并且与化疗耐药相关。我们研究了SCLC中BCL-2上调所涉及的信号通路，以及使用26S蛋白酶体抑制剂硼替佐米抑制核因子κB是否对BCL-2水平或细胞凋亡有任何影响。BCL-2启动子中核因子κB位点的突变使启动子活性降低至野生型启动子的20%以下。硼替佐米治疗导致BCL-2启动子转录减少、BCL-2水平降低并诱导细胞凋亡。这些数据为进一步研究硼替佐米治疗SCLC提供了必要的实验室背景。
