Negative regulation of fibroblast growth factor 10 (FGF-10) by polyoma enhancer activator 3 (PEA3).
Negative regulation of fibroblast growth factor 10 (FGF-10) by polyoma enhancer activator 3 (PEA3).
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DOI：
10.1016/j.ejcb.2009.01.004
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发表时间：
2009-07
影响因子：
6.6
通讯作者：
Grose, Richard
中科院分区：
文献类型：
--
作者：
Chioni, Athina-Myrto;Grose, Richard
FGF-10在发育和疾病中发挥重要作用，是FGFR2B调控细胞增殖、迁移和分化的关键配体。异常的FGF信号与肿瘤发生有关，一些癌症研究报告了FGF-10或FGFR2B上调或Fgfr2激活突变。我们使用5 ' RACE鉴定了小鼠Fgf-10的一个新的转录起始位点。传统的硅分析预测了该位点上游转录因子PEA3的多个结合位点。结合通过染色质免疫沉淀证实，并通过RNAi敲除和PEA3的短暂过表达来研究其功能意义。PEA3敲低导致Fgf-10表达增加，而PEA3过表达导致Fgf-10表达降低。因此，我们已经确定PEA3在小鼠细胞系中是Fgf-10表达的负调节因子，并证实PEA3在人乳腺癌细胞系（MCF-7和MDA-MB-231）中也有活性。此外，PEA3在这些细胞中的过度表达导致细胞迁移受损，FGF-10治疗可以挽救细胞迁移。因此，PEA3可以调节Fgf-10的转录，这种调节可以控制乳腺癌细胞的行为。
FGF-10 plays an important role in development and disease, acting as the key ligand for FGFR2B to regulate cell proliferation, migration and differentiation. Aberrant FGF signalling is implicated in tumourigenesis, with several cancer studies reporting FGF-10 or FGFR2B upregulation or identifying activating mutations in Fgfr2. We used 5’ RACE to identify a novel transcription start site for murine Fgf-10. Conventional in silico analysis predicted multiple binding sites for the transcription factor PEA3 upstream of this site. Binding was confirmed by chromatin immunopreciptation, and functional significance was studied by both RNAi knockdown and transient over-expression of PEA3. Knockdown of PEA3 message led to increased Fgf-10 expression, whereas overexpression of PEA3 resulted in decreased Fgf-10 expression. Thus, we have identified PEA3 as a negative regulator of Fgf-10 expression in a murine cell line and confirmed that activity also is seen in human breast cancer cell lines (MCF-7 and MDA-MB-231). Furthermore, over-expression of PEA3 in these cells resulted in impaired cell migration, which was rescued by treatment with FGF-10. Thus, PEA3 can regulate the transcription of Fgf-10 and such modulation can control breast cancer cell behaviour.
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DOI：
10.1073/pnas.88.12.5096
发表时间：
1991-06-01
影响因子：
11.1
作者：
JAT, PS;NOBLE, MD;KIOUSSIS, D
通讯作者：
KIOUSSIS, D
影响因子：
3.8
作者：
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3.5
作者：
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11.4
作者：
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DOI：
10.1098/rstb.2004.1464
发表时间：
2004-05-29
影响因子：
6.3
作者：
Braun, S;Keller, UAD;Werner, S
通讯作者：
Werner, S