Lysine-specific histone demethylase 1 inhibitors control breast cancer proliferation in ERα-dependent and -independent manners.
Lysine-specific histone demethylase 1 inhibitors control breast cancer proliferation in ERα-dependent and -independent manners.
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DOI：
10.1021/cb300108c
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发表时间：
2012-07-20
影响因子：
4
通讯作者：
McCafferty, Dewey G.
中科院分区：
文献类型：
--
作者：
Pollock, Julie A.;Larrea, Michelle D.;Jasper, Jeff S.;McDonnell, Donald P.;McCafferty, Dewey G.
赖氨酸特异性脱甲基酶1（LSD 1，也称为KDM 1）是一种组蛋白修饰酶，可调节许多在癌症进展和增殖中重要的基因的表达。它存在于各种转录复合物中，包括含有雌激素受体（ER）的那些。事实上，LSD 1活性和/或表达的抑制已显示在体外减弱乳腺癌细胞中的雌激素信号传导，这暗示该蛋白质在癌症的发病机制中。在此，我们描述了利用小分子抑制剂苯环丙胺类，沿着小干扰RNA来探测LSD 1在乳腺癌增殖和雌激素依赖性基因转录中的作用的实验。令人惊讶的是，尽管我们已经证实LSD 1的抑制强烈抑制乳腺癌细胞的增殖，但我们已经确定LSD 1抑制的细胞抑制作用不受ER状态的影响。这些数据表明，LSD 1可能是几种类型的乳腺癌中有用的治疗靶点;最值得注意的是，LSD 1的抑制剂可能在治疗ER阴性癌症中具有实用性，对于这些癌症，存在最少的治疗选择。
Lysine specific demethylase 1 (LSD1, also known as KDM1) is a histone modifying enzyme that regulates the expression of many genes important in cancer progression and proliferation. It is present in various transcriptional complexes including those containing the estrogen receptor (ER). Indeed, inhibition of LSD1 activity and or expression has been shown to attenuate estrogen signaling in breast cancer cells in vitro implicating this protein in the pathogenesis of cancer. Herein we describe experiments that utilize small molecule inhibitors, phenylcyclopropylamines, along with small interfering RNA to probe the role of LSD1 in breast cancer proliferation and in estrogen-dependent gene transcription. Surprisingly, whereas we have confirmed that inhibition of LSD1 strongly inhibits proliferation of breast cancer cells, we have determined that the cytostatic actions of LSD1 inhibition are not impacted by ER-status. These data suggest that LSD1 may be a useful therapeutic target in several types of breast cancer; most notably inhibitors of LSD1 may have utility in the treatment of ER-negative cancers for which there are minimal therapeutic options.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
64.5
作者：
Garcia-Bassets, Ivan;Kwon, Young-Soo;Rosenfeld, Michael G.
通讯作者：
Rosenfeld, Michael G.
影响因子：
11.5
作者：
Hoeflich, Klaus P.;O'Brien, Carol;Lackner, Mark R.
通讯作者：
Lackner, Mark R.
影响因子：
3.8
作者：
Huang, Yi;Vasilatos, Shauna N.;Boric, Lamia;Shaw, Patrick G.;Davidson, Nancy E.
通讯作者：
Davidson, Nancy E.
小分子和组蛋白底物类似物作为LSD1赖氨酸脱甲基酶抑制剂的比较分析。
影响因子：
15
作者：
Culhane, Jeffrey C.;Wang, Dongqing;Yen, Paul M.;Cole, Philip A.
通讯作者：
Cole, Philip A.