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p53突变是乳腺癌预后不良的标志。为鉴定p53的下游靶点,我们筛选了两个转录组数据集,包括p53野生型或p53缺失背景的MCF10A乳腺上皮细胞的cDNA微阵列,以及乳腺浸润性癌的RNA测序分析。在此,我们揭示了十个新的p53靶基因候选,它们在野生型细胞中诱导p53后表达上调。这些基因在具有野生型p53的乳腺浸润性癌组织中表达也较高。GO分析发现表皮发育和外胚层发育,COL17A1参与其过程,被野生型p53显著上调。COL17A1在人体乳腺细胞和小鼠乳腺组织中以p53依赖方式表达增强。报告基因和ChIP分析揭示了COL17A1基因内含子中的p53结合序列。基因工程过表达COL17A1产物的MDA-MB-231细胞在体外表现出迁移和侵袭能力降低。同样,COL17A1表达在转移瘤中低于原发瘤及正常组织,即使来自同一患者。此外,高COL17A1表达与乳腺浸润性癌患者较长的生存期相关。总之,我们揭示COL17A1是乳腺组织中p53的新型转录靶标,能抑制细胞迁移和侵袭,且与更好的预后相关。
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Varalee Yodsurang
Chizu Tanikawa
Takafumi Miyamoto
Oncotarget
The University of Tokyo
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Yodsurang等人(周五,)研究了该问题。
www.synapsesocial.com/papers/69dd61f5629747396240cc94 — DOI: https://doi.org/10.18632/oncotarget.18433
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