The role of estrogen receptor β in transplacental cancer prevention by indole-3-carbinol.
The role of estrogen receptor β in transplacental cancer prevention by indole-3-carbinol.
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DOI：
10.1158/1940-6207.capr-12-0311
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发表时间：
2013-04
期刊：
影响因子：
--
通讯作者：
Williams DE
中科院分区：
文献类型：
--
作者：
Benninghoff AD;Williams DE
本研究采用雌激素受体β（ERβ）基因敲除小鼠模型，评价了十字花科蔬菜中重要的生物活性成分吲哚-3-甲醇（I3 C）对环境致癌物二苯并[def，p]金（DBC）宫内暴露子代的预防作用。I3 C通过母体饮食提供，同时在妊娠期间暴露于致癌物，或直接在开始使用DBC后提供给后代。I3 C仅在通过母体饮食提供时才能有效降低后代T细胞急性淋巴细胞性淋巴瘤/白血病（T-ALL）相关死亡率，尽管ERβ在介导这种反应中的作用存在明显的性别差异。在雌性后代中，通过母体膳食I3 C化学预防T-ALL需要ERβ表达; Esr 2野生型和杂合子雌性后代的存活率>90%，而Esr 2缺失雌性后代的存活率为66%。或者，ERβ状态对雄性动物中I3 C的经胎盘化学预防作用无显著影响。ERβ在介导肺癌发生或I3 C化学预防中的可能作用同样复杂。两种饮食干预均未改变肺肿瘤发生率，而与野生型和杂合型对应物相比，对照饮食的Esr 2缺失雌性动物的肺肿瘤多样性大幅降低，通过母体饮食暴露于I3 C的Esr 2缺失雄性动物的肺肿瘤多样性略低。这些发现表明，I3 C可能通过ERβ起作用，以防止或抑制DBC引发的经胎盘致癌作用，但这种受体的参与似乎取决于癌症类型和后代的性别。
In the present study, the efficacy of indole-3-carbinol (I3C), a key bioactive component of cruciferous vegetables, for prevention of cancer in offspring exposed in utero to the environmental carcinogen dibenzo[def,p]chrysene (DBC) was evaluated using an estrogen receptor beta (ERβ) knockout mouse model. I3C was provided either through the maternal diet coincident with carcinogen exposure during pregnancy or directly to offspring post initiation with DBC. I3C was effective at reducing T-cell acute lymphoblastic lymphoma/leukemia (T-ALL)-related mortality in offspring only if provided via the maternal diet, although a gender difference in the role of ERβ in mediating this response was evident. In female offspring, chemoprevention of T-ALL by maternal dietary I3C required expression of ERβ; survival in Esr2 wild-type and heterozygous female offspring was >90% compared to 66% in Esr2 null females. Alternatively, ERβ status did not significantly impact the transplacental chemoprevention by I3C in males. The possible role of ERβ in mediating lung carcinogenesis or chemoprevention by I3C was similarly complicated. Lung tumor incidence was unaltered by either dietary intervention, whereas lung tumor multiplicity was substantially reduced in Esr2 null females on the control diet and marginally lower in Esr2 null males exposed to I3C via the maternal diet compared to their wild-type and heterozygous counterparts. These findings suggest that I3C may act via ERβ to prevent or suppress DBC-initiated transplacental carcinogenesis, but that the involvement of this receptor appears to differ depending on the cancer type and gender of the offspring.