Regulation of cell cycle and RNA transcription genes identified by microarray analysis of PC-3 human prostate cancer cells treated with luteolin.
Regulation of cell cycle and RNA transcription genes identified by microarray analysis of PC-3 human prostate cancer cells treated with luteolin.
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DOI：
10.1016/j.jsbmb.2009.09.016
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发表时间：
2010-01
影响因子：
4.1
通讯作者：
Markaverich, Barry M.
中科院分区：
文献类型：
--
作者：
Shoulars, Kevin;Rodriguez, Mary Ann;Thompson, Trellis;Markaverich, Barry M.
前列腺癌是美国男性癌症相关死亡的第二大原因。我们以前的研究表明，核型雌二醇结合部位的配体，如木犀草素，在体内外对前列腺癌细胞具有显著的抑制作用；然而，这些配体在细胞生长和增殖中的作用尚不清楚。为了进一步阐明木犀草素作用于PC-3细胞的分子机制，我们对38,500个基因进行了cRNA微阵列分析，以确定木犀草素处理后发生改变的基因。木犀草素处理后，3331个基因的表达发生了1.2倍以上的变化。对改变的基因的分析确定了木犀草素显著影响的两条途径。细胞周期途径包括22个下调的基因(包括Polo-like kinase1、Cyclin A2、Cyclin E2和增殖细胞核抗原)和一个上调的基因(Cyclin依赖的激酶抑制物1B)。此外，在RNA转录途径中，木犀草素下调了13个基因的表达。实时聚合酶链式反应和免疫印迹验证了微阵列的观察结果。此外，两种人工合成的、化学上不同的II型配体，ZN-2和BMHPC，在mRNA和蛋白质水平上模拟了木犀草素对PC-3细胞基因表达的影响。最后，染色质免疫沉淀分析表明，木犀草素通过改变启动子相关组蛋白的乙酰化状态而对基因产生影响。综上所述，这些数据表明，II型配体通过表观遗传控制参与细胞周期进展和RNA转录的关键基因来抑制细胞的生长和增殖。
Prostate cancer is the second leading cause of cancer-related deaths in men in the United States. Our previous studies have shown that ligands for the nuclear type II [3H]estradiol binding site such as luteolin significantly inhibit prostate cancer cells in vitro and in vivo; however, the role of these ligands in cell growth and proliferation is poorly understood. In order to further elucidate the molecular mechanism through which luteolin exerts its effects on PC-3 cells, cRNA microarray analyses was performed on 38,500 genes to determine the genes altered by luteolin treatment. The expression of 3,331 genes was changed greater than 1.2-fold after luteolin treatment. Analysis of the altered genes identified two pathways that were significantly affected by luteolin. The Cell Cycle Pathway contained 22 down-regulated genes (including polo-like kinase 1, cyclin A2, cyclin E2 and proliferation cell nuclear antigen) and one up-regulated gene (cyclin-dependent kinase inhibitor 1B). In addition, 13 genes were down-regulated by luteolin in the RNA Transcription Pathway. Real-time polymerase chain reactions and western blots verified the observations from the microarray. In addition, two synthetic, chemically distinct type II ligands, ZN-2 and BMHPC, mimicked the effects of luteolin on gene expression at the mRNA and protein level in PC-3 cells. Finally, chromatin immunoprecipitation assays indicated that luteolin exerts its effects on genes by altering the acetylation state of promoter-associated histones. Taken together, the data suggest that type II ligands inhibit cell growth and proliferation through epigenetic control of key genes involved in cell cycle progression and RNA transcription.
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DOI：
10.1073/pnas.011404098
发表时间：
2001-01-02
影响因子：
11.1
作者：
Li, C;Wong, WH
通讯作者：
Wong, WH
影响因子：
6.6
作者：
LAROCCA, LM;GIUSTACCHINI, M;CAPELLI, A
通讯作者：
CAPELLI, A
影响因子：
3.5
作者：
CARBONE, A;RANELLETTI, FO;CAPELLI, A
通讯作者：
CAPELLI, A
影响因子：
10.3
作者：
LEAV, I;HO, SM;DAMASSA, D
通讯作者：
DAMASSA, D
DOI：
10.1016/0960-0760(94)00170-q
发表时间：
1995-03-01
影响因子：
4.1
作者：
HO, SM;YU, M
通讯作者：
YU, M