Department of Clinical Laboratory Center, Affiliated Hospital of Nantong University, Nantong, China.
Neoplasma. 2012;59(3):341-7. doi: 10.4149/neo_2012_044.
A proliferation-inducing ligand (APRIL) which stimulates the cell proliferation is abundantly expressed in colorectal cancer (CRC) tumors. In this report, the promoter region of the APRIL gene was determined and the major transcription factor was investigated for the first time. Deletion analysis of 5'-flanking region of the human APRIL gene and transient transfection revealed that a 538 bp region (from -1539 to -1001) was essential for promoter activation of the APRIL gene. The data from electrophoretic mobility shift assays (EMSA) indicated that the 538 bp promoter region was responsive to the specificity protein 1 (Sp1) and nuclear factor kappa B (NF-kB). Overexpression of Sp1 or NF-kB increased the activity of the APRIL promoter. Mithramycin A (inhibitor of Sp1) and Bay11-7082 (inhibitor of NF-kB) exhibited an inhibitory activity to APRIL promoter. Our results will benefit to the APRIL gene regulation investigation and contribute to discover new drug target for the APRIL gene therapy of CRC.
增殖诱导配体（APRIL）可刺激细胞增殖，在结直肠癌（CRC）肿瘤中大量表达。在本报告中，首次确定了 APRIL 基因的启动子区域，并研究了主要的转录因子。人 APRIL 基因 5'侧翼区的缺失分析和瞬时转染表明，-1539 至-1001 位的 538bp 区域对于 APRIL 基因启动子的激活是必需的。电泳迁移率变动分析（EMSA）的数据表明，538bp 启动子区域对特异性蛋白 1（Sp1）和核因子 kappa B（NF-kB）有反应。Sp1 或 NF-kB 的过表达增加了 APRIL 启动子的活性。米托蒽醌 A（Sp1 抑制剂）和 Bay11-7082（NF-kB 抑制剂）对 APRIL 启动子表现出抑制活性。我们的研究结果将有助于 APRIL 基因调控的研究，并有助于发现 CRC 的 APRIL 基因治疗的新药物靶点。
