A potential estrogen mimetic effect of a bis(ethyl)polyamine analogue on estrogen receptor positive MCF-7 breast cancer cells
A potential estrogen mimetic effect of a bis(ethyl)polyamine analogue on estrogen receptor positive MCF-7 breast cancer cells
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双（乙基）多胺类似物对雌激素受体阳性 MCF-7 乳腺癌细胞的潜在雌激素模拟作用
DOI：
10.1007/s00726-011-1005-0
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发表时间：
2012
期刊：
影响因子：
3.5
通讯作者：
Thomas TJ
中科院分区：
文献类型：
--
作者：
Nayvelt I;John S;Hsu HC;Yang P;Liu W;Das G;Hyvonen MT;Alhonen L;Keinanen TA;Shirahata A;Patel R;Thomas T;Thomas TJ
BE-3 - 3 - 3 - 3（1，15-（乙氨基）4，8，12-三氮杂十五烷）是一种双（乙基）多胺类似物，正在研究作为乳腺癌的治疗剂。由于雌二醇（E2）是乳腺癌生长中的关键调节分子，我们研究了在存在和不存在E2的情况下BE-3 - 3 - 3 - 3对雌激素受体α（ER α）阳性MCF-7细胞的影响。在E2存在下，使用[3H]-胸苷掺入试验观察到DNA合成的浓度依赖性降低。在不存在E2的情况下，低浓度（2.5 - 10 μ M）的BE-3 - 3 - 3在24和48 h时增加[3H]-胸苷掺入。BE-3 - 3 - 3 - 3诱导早期反应基因c-mycandc-fos的表达，在不存在E2的情况下，但在其存在下，通过实时定量聚合酶链反应（qPCR）测定。BE-3 - 3 - 3 - 3对ER α阴性细胞系MDA-MB-231中的这些基因无显著影响。染色质免疫沉淀实验表明，雌激素受体及其辅激活子SRC-3（steroid receptor co-activator 3）对雌激素敏感基因epS2/Tff1启动子的占据作用增强。BE-3 - 3 - 3 - 3处理的细胞的共聚焦显微镜显示ER α的膜定位，与E2诱导的相似。BE-3 - 3 - 3 - 3抑制细胞增殖的失败与自噬空泡形成以及Beclin 1和MAP LC 3 II的诱导有关。这些结果表明，BE-3 - 3 - 3 - 3在不存在和存在E2的情况下对MCF-7细胞的不同作用，并表明多胺类似物的临床前和临床开发可能需要特别的预防措施和选择敏感的患者亚群。
BE-3-3-3-3 (1,15-(ethylamino)4,8,12-triazapentadecane) is a bis(ethyl)polyamine analogue under investigation as a therapeutic agent for breast cancer. Since estradiol (E2) is a critical regulatory molecule in the growth of breast cancer, we examined the effect of BE-3-3-3-3 on estrogen receptor α (ERα) positive MCF-7 cells in the presence and absence of E2. In the presence of E2, a concentration-dependent decrease in DNA synthesis was observed using [3H]-thymidine incorporation assay. In the absence of E2, low concentrations (2.5–10 μM) of BE-3-3-3-3 increased [3H]-thymidine incorporation at 24 and 48 h. BE-3-3-3-3 induced the expression of early response genes,c-mycandc-fos, in the absence of E2, but not in its presence, as determined by real-time quantitative polymerase chain reaction (qPCR). BE-3-3-3-3 had no significant effect on these genes in an ERα-negative cell line, MDA-MB-231. Chromatin immunoprecipitation assay demonstrated enhanced promoter occupation by either E2or BE-3-3-3-3 of an estrogen-responsive genepS2/Tff1by ERα and its co-activator, steroid receptor co-activator 3 (SRC-3). Confocal microscopy of BE-3-3-3-3-treated cells revealed membrane localization of ERα, similar to that induced by E2. The failure of BE-3-3-3-3 to inhibit cell proliferation was associated with autophagic vacuole formation, and the induction of Beclin 1 and MAP LC3 II. These results indicate a differential effect of BE-3-3-3-3 on MCF-7 cells in the absence and presence of E2, and suggest that pre-clinical and clinical development of polyamine analogues might require special precautions and selection of sensitive subpopulation of patients.
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双（乙基）多胺类似物对 FVB/NTgN (MMTVneu) 转基因小鼠乳腺肿瘤发展的抗肿瘤作用。
影响因子：
9.7
作者：
Shah,N;Antony,T;Haddad,S;Amenta,P;Shirahata,A;Thomas,TJ;Thomas,T
通讯作者：
Thomas,T
影响因子：
3
作者：
Thresia Thomas;M. Gallo;T. Thomas
通讯作者：
Thresia Thomas;M. Gallo;T. Thomas
雌二醇对 MCF-7 乳腺癌细胞中鸟氨酸脱羧酶 mRNA、酶活性和多胺水平的控制：治疗意义
影响因子：
3.8
作者：
T. Thomas;T. Thomas
通讯作者：
T. Thomas
影响因子：
11.2
作者：
Diane E. McCloskey;R. Casero;P. Woster;N. Davidson
通讯作者：
Diane E. McCloskey;R. Casero;P. Woster;N. Davidson
影响因子：
3.4
作者：
Streiff, RR;Bender, JF
通讯作者：
Bender, JF