Yin Yang 1 cooperates with activator protein 2 to stimulate ERBB2 gene expression in mammary cancer cells
Yin Yang 1 cooperates with activator protein 2 to stimulate ERBB2 gene expression in mammary cancer cells
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DOI：
10.1074/jbc.m503790200
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发表时间：
2005-07-01
影响因子：
4.8
通讯作者：
Winkler, R
中科院分区：
文献类型：
--
作者：
Begon, DY;Delacroix, L;Winkler, R
ERBB2癌基因的过表达在约30%的乳腺癌中观察到，并且通常与不良预后相关。我们和其他实验室的先前结果表明，转录活性升高显著促进乳腺癌细胞系中ERBB 2 mRNA的过表达。激活蛋白2（AP-2）转录因子通过位于转录起始位点上游215和500 bp的两个识别序列来解释这种过表达。此外，AP-2转录因子在过表达ERBB 2的癌细胞系中高度表达。在这份报告中，我们研究了阴阳1号（YY 1）对AP-2诱导的ERBB 2启动子活性激活的协同作用。我们在乳腺癌细胞系中检测到高水平的YY1转录因子。值得注意的是，我们发现YY1在HepG2和HCT 116细胞中都通过AP-2位点增强ERBB 2启动子的AP-2 α转录激活，而羧基末端截短形式的YY1不能.此外，我们证明了内源性AP-2和YY 1因子在BT-474乳腺癌细胞系中的相互作用。此外，内源性YY1蛋白的反义抑制降低了AP-2反应ERBB2报告质粒在BT-474乳腺癌细胞中的转录。最后，我们在染色质免疫沉淀试验中检测了ERBB2近端启动子的体内AP-2和YY 1占有率。因此，我们的数据提供的证据表明，YY1与AP 2合作，刺激ERBB2启动子活性，通过AP-2结合位点。
Overexpression of the ERBB2 oncogene is observed in about 30% of breast cancers and is generally correlated with a poor prognosis. Previous results from our and other laboratories indicated that elevated transcriptional activity contributes significantly to the overexpression of ERBB2 mRNA in mammary adenocarcinoma cell lines. Activator protein 2 (AP-2) transcription factors account for this overexpression through two recognition sequences located 215 and 500 bp upstream from the transcription start site. Furthermore, AP-2 transcription factors are highly expressed in cancer cell lines overexpressing ERBB2. In this report, we examined the cooperative effect of Yin Yang 1 (YY1) on AP-2-induced activation of ERBB2 promoter activity. We detected high levels of YY1 transcription factor in mammary cancer cell lines. Notably, we showed that YY1 enhances AP-2 alpha transcriptional activation of the ERBB2 promoter through an AP-2 site both in HepG2 and in HCT116 cells, whereas a carboxyl- terminal- truncated form of YY1 cannot. Moreover, we demonstrated the interaction between endogenous AP-2 and YY1 factors in the BT-474 mammary adenocarcinoma cell line. In addition, inhibition of endogenous YY1 protein by an antisense decreased the transcription of an AP-2-responsive ERBB2 reporter plasmid in BT-474 breast cancer cells. Finally, we detected in vivo AP-2 and YY1 occupancy of the ERBB2 proximal promoter in chromatin immunoprecipitation assays. Our data thus provide evidence that YY1 cooperates with AP2 to stimulate ERBB2 promoter activity through the AP-2 binding sites.