乳腺癌细胞中抑癌基因 HIC1 的缺失导致β2 肾上腺素能受体（ADRB2）失调，进而促进应激诱导的迁移和侵袭。
Loss of Hypermethylated in Cancer 1 (HIC1) in breast cancer cells contributes to stress-induced migration and invasion through β-2 adrenergic receptor (ADRB2) misregulation.
机构信息
CNRS UMR 8161, CNRS-Université de Lille 1-Institut Pasteur de Lille, Lille 59021, France.
出版信息
J Biol Chem. 2012 Feb 17;287(8):5379-89. doi: 10.1074/jbc.M111.304287. Epub 2011 Dec 22.
Abstract
The transcriptional repressor HIC1 (Hypermethylated in Cancer 1) is a tumor suppressor gene inactivated in many human cancers including breast carcinomas. In this study, we show that HIC1 is a direct transcriptional repressor of β-2 adrenergic receptor (ADRB2). Through promoter luciferase activity, chromatin immunoprecipitation (ChIP) and sequential ChIP experiments, we demonstrate that ADRB2 is a direct target gene of HIC1, endogenously in WI-38 cells and following HIC1 re-expression in breast cancer cells. Agonist-mediated stimulation of ADRB2 increases the migration and invasion of highly malignant MDA-MB-231 breast cancer cells but these effects are abolished following HIC1 re-expression or specific down-regulation of ADRB2 by siRNA treatment. Our results suggest that early inactivation of HIC1 in breast carcinomas could predispose to stress-induced metastasis through up-regulation of the β-2 adrenergic receptor.
摘要
转录抑制剂 HIC1（癌症中高甲基化 1）是一种肿瘤抑制基因，在许多人类癌症中失活，包括乳腺癌。在这项研究中，我们表明 HIC1 是β-2 肾上腺素能受体（ADRB2）的直接转录抑制剂。通过启动子荧光素酶活性、染色质免疫沉淀（ChIP）和连续 ChIP 实验，我们证明 ADRB2 是 HIC1 的直接靶基因，在 WI-38 细胞中内源性存在，并且在乳腺癌细胞中 HIC1 重新表达后也是如此。激动剂介导的 ADRB2 刺激增加高度恶性 MDA-MB-231 乳腺癌细胞的迁移和侵袭，但这些效应在 HIC1 重新表达或通过 siRNA 处理特异性下调 ADRB2 后被消除。我们的结果表明，乳腺癌中 HIC1 的早期失活可能通过β-2 肾上腺素能受体的上调导致应激诱导的转移易感性。
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Loss of Hypermethylated in Cancer 1 (HIC1) in breast cancer cells contributes to stress-induced migration and invasion through β-2 adrenergic receptor (ADRB2) misregulation.乳腺癌细胞中抑癌基因 HIC1 的缺失导致β2 肾上腺素能受体（ADRB2）失调，进而促进应激诱导的迁移和侵袭。
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本文引用的文献
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The receptor tyrosine kinase EphA2 is a direct target gene of hypermethylated in cancer 1 (HIC1).受体酪氨酸激酶 EphA2 是癌症中高甲基化 1（HIC1）的直接靶基因。
J Biol Chem. 2012 Feb 17;287(8):5366-78. doi: 10.1074/jbc.M111.329466. Epub 2011 Dec 19.
2
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Oncotarget. 2010 Nov;1(7):628-638. doi: 10.18632/oncotarget.197.
3
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4
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5
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6
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