cAMP responsive element binding protein-1 is a transcription factor of lysosomal-associated protein transmembrane-4 Beta in human breast cancer cells.
cAMP responsive element binding protein-1 is a transcription factor of lysosomal-associated protein transmembrane-4 Beta in human breast cancer cells.
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cAMP 响应元件结合蛋白-1 是人乳腺癌细胞中溶酶体相关蛋白跨膜-4 β 的转录因子。
DOI：
10.1371/journal.pone.0057520
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zhang QY
中科院分区：
文献类型：
--
作者：
Zhang M;Xu JJ;Zhou RL;Zhang QY
溶酶体相关蛋白跨膜4 β（Lysosomal-associated protein transmembrane-4 beta，LAPTM 4 B）是一种潜在的原癌基因，其过表达与肿瘤的发生、发展有关。其转录物在包括乳腺癌在内的各种类型的实体瘤中上调。但其转录调控机制尚不清楚。为了研究LAPTM 4 B在人乳腺癌细胞中的转录调控机制，通过PCR扩增构建了一系列荧光素酶报告基因构建体和cAMP应答元件结合蛋白1（CREB 1）结合位点突变的构建体，并瞬时转染乳腺癌细胞，测定不同启动子区域的转录活性。其中+10的292启动子区转录活性最高。通过电泳迁移率变动分析、超迁移和RNA干扰实验证实CREB 1结合LAPMT 4 B启动子的能力。我们的研究确定了负责LAPTM 4 B组成型表达的核心启动子区域，并阐明CREB 1在人乳腺癌细胞中LAPTM 4 B转录调控中发挥重要作用。
Lysosomal-associated protein transmembrane-4 beta (LAPTM4B) is a potential proto-oncogene, whose overexpression is involved in cancer occurrence and progression. Its transcript is up-regulated in various types of solid tumors including breast cancer. However, its transcriptional regulation mechanism is still unclear. To investigate the mechanism of transcriptional regulation of LAPTM4B in human breast cancer cells, a series of luciferase reporter constructs and construct with mutated binding site for cAMP responsive element binding protein-1 (CREB1) were generated by PCR amplification and transiently transfected into breast cancer cells to determine the transcriptional activities of different promoter regions. The +10∼+292 promoter region was possessed the highest transcriptional activity. The ability of CREB1 to bind the LAPMT4B promoter was confirmed by electrophoretic mobility shift assay, super-shift and RNA interference experiments. Our study identified the core promoter region responsible for constitutive expression of LAPTM4B and clarified that CREB1 played an important role in LAPTM4B transcriptional regulation in human breast cancer cells.
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