Transformation of MCF-10A human breast epithelial cells by zeranol and estradiol-17beta.
Transformation of MCF-10A human breast epithelial cells by zeranol and estradiol-17beta.
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DOI：
10.1111/j.1075-122x.2004.21410.x
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发表时间：
2004-11-01
期刊：
影响因子：
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通讯作者：
Lin, Young C
中科院分区：
文献类型：
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作者：
Liu, Suling;Lin, Young C
在与乳腺癌相关的内分泌因素中，雌激素被认为在人类乳腺癌的发生中起着核心作用。长期接触雌激素会增加患乳腺癌的风险。Zeranol （Ralgro）是一种具有雌激素活性的非甾体药物，在美国牛肉和小牛肉工业中用作生长促进剂。为了确定zeranol和estradiol-17beta是否在人乳腺肿瘤转化中发挥作用，并比较zeranol与estradiol-17beta在人乳腺中的雌激素效能，我们用不同剂量的zeranol或estradiol-17beta治疗人乳腺上皮细胞MCF-10A 10个重复治疗周期。通过倍增时间实验、软琼脂实验和逆转录聚合酶链反应（RT-PCR）实验，我们发现10个重复的雌二醇-17beta或zeranol处理周期可以使MCF-10A细胞的倍增时间减少30 - 40%，并刺激软琼脂中的集落形成，诱导雌激素受体β (er - β) mRNA的表达，这些都在我们的测试剂量范围内无关。此外，我们通过RT-PCR发现zeranol和estradiol-17beta在刺激和抑制人乳腺癌细胞系MCF-7基因表达方面具有相似的效力。这些结果表明，zeranol和estradiol-17 β在长期暴露下均可通过氧化还原（redox）途径和/或er - β介导途径诱导人乳腺上皮细胞肿瘤转化，其效力相似。
Among the endocrine factors associated with breast cancer, estrogens are considered to play a central role in human breast carcinogenesis. Breast cancer risks are increased by long-term exposure to estrogens. Zeranol (Ralgro) is a nonsteroidal agent with estrogenic activity that is used as a growth promoter in the U.S. beef and veal industry. To determine whether zeranol and estradiol-17beta play a role in the neoplastic transformation of human breast and to compare the estrogenic potency of zeranol to that of estradiol-17beta in human breast, we treated human breast epithelial cell MCF-10A with different doses of zeranol or estradiol-17beta for 10 repeated treatment cycles. By utilizing the doubling time assay, soft agar assay, and reverse transcriptase polymerase chain reaction (RT-PCR) assay, we showed that 10 repeated estradiol-17beta or zeranol treatment cycles to MCF-10A cells decrease the doubling time of the cells by 30 to 40% and stimulate colony formation in soft agar and induce estrogen receptor beta (ER-beta) mRNA expression, all of which are not dose related in our tested dose range. Furthermore, we show that zeranol and estradiol-17beta have a similar potency in the stimulation and inhibition of gene expressions in human breast cancer cell line MCF-7 by RT-PCR. These results indicate that both zeranol and estradiol-17beta can induce human breast epithelial cell neoplastic transformation with similar potency in the long-term exposure through the oxidation-reduction (redox) pathway and/or ER-beta-mediated pathway.