BRCA1 and BRCA2 as molecular targets for phytochemicals indole-3-carbinol and genistein in breast and prostate cancer cells.
BRCA1 and BRCA2 as molecular targets for phytochemicals indole-3-carbinol and genistein in breast and prostate cancer cells.
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BRCA1和BRCA2作为植物化学物质吲哚-3-甲醇的分子靶标和乳腺癌细胞中的染料黄酮。
DOI：
10.1038/sj.bjc.6602935
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发表时间：
2006-02-13
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
Indole-3-carbinol (I3C) 和金雀异黄素是分别从十字花科蔬菜和大豆中提取的天然化学物质，对激素反应性肿瘤（例如乳腺癌和前列腺癌）具有潜在的癌症预防活性。此前，我们发现 I3C 诱导 BRCA1 表达，并且 I3C 和 BRCA1 均抑制人乳腺癌细胞中雌激素 (E2) 刺激的雌激素受体 (ER-α) 活性。我们现在报道，I3C 和金雀异黄素均以时间和剂量依赖性方式诱导乳腺癌（MCF-7 和 T47D）和前列腺（DU-145 和 LNCaP）癌细胞类型中乳腺癌易感基因（BRCA1 和 BRCA2）的表达。 BRCA 基因的诱导发生在低剂量的 I3C (20μM) 和金雀异黄素 (0.5–1.0μM) 下，表明与癌症预防的潜在相关性。 I3C 和金雀异黄素的组合对 BRCA 表达的诱导作用强于预期。使用小干扰 RNA (siRNA) 和 BRCA 表达载体的研究表明，BRCA2 的植物化学诱导部分归因于 BRCA1。功能研究表明，I3C 介导的细胞毒性部分取决于 BRCA1 和 BRCA2。 I3C 和金雀异黄素对 E2 刺激的 ER-α 活性的抑制依赖于 BRCA1； BRCA1-siRNA 部分逆转了 I3C 和金雀异黄素对配体诱导型雄激素受体 (AR) 活性的抑制作用。最后，我们提供的证据表明 BRCA1 表达的植物化学诱导部分归因于内质网应激反应信号传导。这些发现表明 BRCA 基因是 I3C 和金雀异黄素某些活性的分子靶标。
Indole-3-carbinol (I3C) and genistein are naturally occurring chemicals derived from cruciferous vegetables and soy, respectively, with potential cancer prevention activity for hormone-responsive tumours (e.g., breast and prostate cancers). Previously, we showed that I3C induces BRCA1 expression and that both I3C and BRCA1 inhibit oestrogen (E2)-stimulated oestrogen receptor (ER-α) activity in human breast cancer cells. We now report that both I3C and genistein induce the expression of both breast cancer susceptibility genes (BRCA1 and BRCA2) in breast (MCF-7 and T47D) and prostate (DU-145 and LNCaP) cancer cell types, in a time- and dose-dependent fashion. Induction of the BRCA genes occurred at low doses of I3C (20 μM) and genistein (0.5–1.0 μM), suggesting potential relevance to cancer prevention. A combination of I3C and genistein gave greater than expected induction of BRCA expression. Studies using small interfering RNAs (siRNAs) and BRCA expression vectors suggest that the phytochemical induction of BRCA2 is due, in part, to BRCA1. Functional studies suggest that I3C-mediated cytoxicity is, in part, dependent upon BRCA1 and BRCA2. Inhibition of E2-stimulated ER-α activity by I3C and genistein was dependent upon BRCA1; and inhibition of ligand-inducible androgen receptor (AR) activity by I3C and genistein was partially reversed by BRCA1-siRNA. Finally, we provide evidence suggesting that the phytochemical induction of BRCA1 expression is due, in part, to endoplasmic reticulum stress response signalling. These findings suggest that the BRCA genes are molecular targets for some of the activities of I3C and genistein.
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影响因子：
4.2
作者：
Lamartiniere, CA;Cotroneo, MS;Elgavish, A
通讯作者：
Elgavish, A
影响因子：
5.3
作者：
Bruhat, A;Jousse, C;Fafournoux, P
通讯作者：
Fafournoux, P
影响因子：
4.8
作者：
Kuiper, GGJM;Lemmen, JG;Gustafsson, JÄ
通讯作者：
Gustafsson, JÄ
影响因子：
8
作者：
Fan, SJ;Ma, YX;Rosen, EM
通讯作者：
Rosen, EM
影响因子：
4.7
作者：
Cabanes, A;Wang, M;Hilakivi-Clarke, L
通讯作者：
Hilakivi-Clarke, L