Comparison of the effects of phenethyl isothiocyanate and sulforaphane on gene expression in breast cancer and normal mammary epithelial cells.
Comparison of the effects of phenethyl isothiocyanate and sulforaphane on gene expression in breast cancer and normal mammary epithelial cells.
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DOI：
10.3181/0808-rm-241
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发表时间：
2009-03
期刊：
影响因子：
--
通讯作者：
Morris ME
中科院分区：
文献类型：
--
作者：
Telang U;Brazeau DA;Morris ME
异硫氰酸苯乙酯（PEITC）和萝卜硫素（SF）在肺癌、前列腺癌、乳腺癌和结肠癌中表现出肿瘤预防活性。我们的目的是研究这两种异硫氰酸酯对雌激素受体相关基因的影响，以及雌激素依赖性乳腺癌细胞系MCF 7和正常人乳腺上皮细胞（HME）中与凋亡和细胞周期相关的基因。我们用0.3 μ M或3.0 μ M浓度的PEITC或SF处理细胞。在HME细胞中，PEITC在0.3 μ M浓度下显著改变了23个基因的基因表达，在3.0 μ M浓度下显著改变了4个基因的基因表达。SF在0.3 μ M浓度下改变了16个基因的表达，在3.0 μ M浓度下改变了2个基因的表达。在HME细胞中，由PEITC和SF改变的基因表现出在程度和变化方向上相似的基因表达变化。在MCF-7细胞中，PEITC在两种处理水平下均未产生基因表达的任何显著变化。SF在7个基因中产生显著变化，但仅在3.0 μ M的较高处理水平下。与乳腺癌细胞相比，正常乳腺细胞在雌激素受体相关基因的表达方面表现出更多的变化，并且这些变化主要发生在0.3 μ M的低浓度下，该浓度可通过饮食输入异硫氰酸酯来实现。新的发现是在正常人乳腺细胞中促凋亡基因BAD和雌激素受体β基因的上调。观察到的这些基因改变，沿着肿瘤抑制因子p21和p27的上调，可能为乳腺细胞提供抗乳腺癌的保护作用。
Phenethyl isothiocyanate (PEITC) and sulforaphane (SF) exhibit tumor preventive activity in lung, prostate, breast and colon cancers. Our objective was to examine the effect of these two isothiocyanates on estrogen receptor-related genes, and genes related to apoptosis and cell cycle in the estrogen-dependent breast cancer cell line MCF7 and in normal human epithelial breast (HME) cells. We treated cells with 0.3 μM or 3.0 μM concentrations of PEITC or SF. In HME cells, gene expression was significantly altered for 23 genes by PEITC at a concentration of 0.3 μM and 4 genes at 3.0 μM. SF altered the expression of 16 genes at a concentration of 0.3 μM and 2 genes at 3.0 μM. In HME cells, genes altered by both PEITC and SF exhibited changes in gene expression that were similar in extent as well as direction of change. In MCF-7 cells, PEITC did not produce any significant changes in the gene expression at both treatment levels. SF produced significant changes in 7 genes, but only at the higher treatment level of 3.0 μM. Normal mammary cells exhibited more changes in the expression of estrogen receptor related genes than did breast cancer cells, and significantly these changes occurred predominantly at the low concentration of 0.3 μM, a concentration achievable by dietary input of isothiocyanates. Novel findings were the upregulation of the pro-apoptotic gene BAD and estrogen receptor beta gene in normal human mammary cells. These gene alterations observed, along with upregulation of tumor suppressors p21 and p27, may provide a protective effect to mammary cells against breast cancer.