Mammalian lysine histone demethylase KDM2A regulates E2F1-mediated gene transcription in breast cancer cells.
Mammalian lysine histone demethylase KDM2A regulates E2F1-mediated gene transcription in breast cancer cells.
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DOI：
10.1371/journal.pone.0100888
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Chellappan S
中科院分区：
文献类型：
--
作者：
Rizwani W;Schaal C;Kunigal S;Coppola D;Chellappan S
It is established that histone modifications like acetylation, methylation, phosphorylation and ubiquitination affect chromatin structure and modulate gene expression. Lysine methylation/demethylation on Histone H3 and H4 is known to affect transcription and is mediated by histone methyl transferases and histone demethylases. KDM2A/JHDM1A/FBXL11 is a JmjC-containing histone demethylase that targets mono- and dimethylated Lys36 residues of Histone H3; its function in breast cancer is not fully understood. Here we show that KDM2A is strongly expressed in myoepithelial cells (MEPC) in breast cancer tissues by immunohistochemistry. Ductal cells from ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) show positive staining for KDM2A, the expression decreases with disease progression to metastasis. Since breast MEPCs have tumor-suppressive and anti-angiogenic properties, we hypothesized that KDM2A could be contributing to some of these functions. Silencing KDM2A with small interfering RNAs demonstrated increased invasion and migration of breast cancer cells by suppressing a subset of matrix metalloproteinases (MMP-2, -9, -14 and -15), as seen by real-time PCR. HUVEC cells showed increased angiogenic tubule formation ability in the absence of KDM2A, with a concomitant increase in the expression of VEGF receptors, FLT-1 and KDR. KDM2A physically bound to both Rb and E2F1 in a cell cycle dependent manner and repressed E2F1 transcriptional activity. Chromatin immunoprecipitation (ChIP) assays revealed that KDM2A associates with E2F1-regulated proliferative promoters CDC25A and TS in early G-phase and dissociates in S-phase. Further, KDM2A could also be detected on MMP9, 14 and 15 promoters, as well as promoters of FLT1 and KDR. KDM2A could suppress E2F1-mediated induction of these promoters in transient transfection experiments. These results suggest a regulatory role for KDM2A in breast cancer cell invasion and migration, through the regulation of E2F1 function.
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影响因子：
37.3
作者：
Hayami S;Yoshimatsu M;Veerakumarasivam A;Unoki M;Iwai Y;Tsunoda T;Field HI;Kelly JD;Neal DE;Yamaue H;Ponder BA;Nakamura Y;Hamamoto R
通讯作者：
Hamamoto R
影响因子：
12.4
作者：
通讯作者：
--
影响因子：
16.8
作者：
Couture, Jean-Francois;Collazo, Evys;Trievel, Raymond C.
通讯作者：
Trievel, Raymond C.
影响因子：
6.4
作者：
Dasgupta, Piyali;Rizwani, Wasia;Pillai, Smitha;Kinkade, Rebecca;Kovacs, Michelle;Rastogi, Shipra;Banerjee, Sarmistha;Carless, Melanie;Kim, Esther;Coppola, Domenico;Haura, Eric;Chellappan, Srikumar
通讯作者：
Chellappan, Srikumar
影响因子：
3.7
作者：
Nijwening JH;Geutjes EJ;Bernards R;Beijersbergen RL
通讯作者：
Beijersbergen RL