Long-term exposure of MCF-7 breast cancer cells to ethanol stimulates oncogenic features.
Long-term exposure of MCF-7 breast cancer cells to ethanol stimulates oncogenic features.
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DOI：
10.3892/ijo.2016.3800
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发表时间：
2017-01
影响因子：
5.2
通讯作者：
Gonzalez-Cadavid NF
中科院分区：
文献类型：
--
作者：
Gelfand R;Vernet D;Bruhn KW;Sarkissyan S;Heber D;Vadgama JV;Gonzalez-Cadavid NF
饮酒是患乳腺癌的一个危险因素。尽管人们认为乙醛或雌激素介导的途径发挥了作用，但对其机制知之甚少。我们先前的研究表明，人正常乳腺上皮细胞株MCF-12A长期暴露于2.5mM乙醇(血液酒精含量~0.012%)中，可诱导上皮间充质转化和致癌转化。在这项研究中，我们在人类乳腺癌细胞系MCF-7中研究了酗酒者类似的酒精暴露浓度是否会增加恶性进展。短期(1周)低至1-5 mM(相当于血液酒精浓度~0.0048-0.024%)的乙醇孵育可上调干细胞相关蛋白Oct4和Nanog的表达，但在25 mM乙醇孵育后，干细胞相关蛋白Oct4和Nanog的表达降低。长期(4周)接触25 mM乙醇可上调Oct4和Nanog蛋白以及肿瘤标志物Ceacam6的表达。DNA芯片分析显示，暴露1周的细胞中，金属硫蛋白基因表达上调，尤其是MT1X。长期暴露可上调某些肿瘤相关基因(STEAP4、SERPINA3、SAMD9、GDF15、KRT15、ITGB6、TP63和PGR，以及CEACAM、干扰素相关和人类白细胞抗原相关基因家族)的表达。其中一些发现得到了RT-PCR的验证。类似的处理也调节了许多microRNAs(MiRs)，包括Oct4的一个调节子，以及参与肿瘤发生和/或恶性肿瘤的miRs，只有少数雌激素诱导的miRs。长期的25 mM乙醇还诱导了5.6倍的锚定非依赖性生长，这是恶性特征的一个指标。暴露在乙醛中，几乎没有或几乎没有乙醇的影响。以前显示的酒精诱导正常乳腺细胞致癌转化的结果现在得到了补充，目前的结果表明酒精可能参与乳腺癌的恶性进展。
Alcohol consumption is a risk factor for breast cancer. Little is known regarding the mechanism, although it is assumed that acetaldehyde or estrogen mediated pathways play a role. We previously showed that long-term exposure to 2.5 mM ethanol (blood alcohol ~0.012%) of MCF-12A, a human normal epithelial breast cell line, induced epithelial mesenchymal transition (EMT) and oncogenic transformation. In this study, we investigated in the human breast cancer cell line MCF-7, whether a similar exposure to ethanol at concentrations ranging up to peak blood levels in heavy drinkers would increase malignant progression. Short-term (1-week) incubation to ethanol at as low as 1–5 mM (corresponding to blood alcohol concentration of ~0.0048–0.024%) upregulated the stem cell related proteins Oct4 and Nanog, but they were reduced after exposure at 25 mM. Long-term (4-week) exposure to 25 mM ethanol upregulated the Oct4 and Nanog proteins, as well as the malignancy marker Ceacam6. DNA microarray analysis in cells exposed for 1 week showed upregulated expression of metallothionein genes, particularly MT1X. Long-term exposure upregulated expression of some malignancy related genes (STEAP4, SERPINA3, SAMD9, GDF15, KRT15, ITGB6, TP63, and PGR, as well as the CEACAM, interferon related, and HLA gene families). Some of these findings were validated by RT-PCR. A similar treatment also modulated numerous microRNAs (miRs) including one regulator of Oct4 as well as miRs involved in oncogenesis and/or malignancy, with only a few estrogen-induced miRs. Long-term 25 mM ethanol also induced a 5.6-fold upregulation of anchorage-independent growth, an indicator of malignant-like features. Exposure to acetaldehyde resulted in little or no effect comparable to that of ethanol. The previously shown alcohol induction of oncogenic transformation of normal breast cells is now complemented by the current results suggesting alcohol's potential involvement in malignant progression of breast cancer.
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影响因子：
5.2
作者：
Gelfand R;Vernet D;Bruhn K;Vadgama J;Gonzalez-Cadavid NF
通讯作者：
Gonzalez-Cadavid NF
影响因子：
9.2
作者：
Boo L;Ho WY;Ali NM;Yeap SK;Ky H;Chan KG;Yin WF;Satharasinghe DA;Liew WC;Tan SW;Ong HK;Cheong SK
通讯作者：
Cheong SK
影响因子：
14.9
作者：
Bhat-Nakshatri P;Wang G;Collins NR;Thomson MJ;Geistlinger TR;Carroll JS;Brown M;Hammond S;Srour EF;Liu Y;Nakshatri H
通讯作者：
Nakshatri H
影响因子：
6.4
作者：
Cimino, Daniela;Fuso, Luca;De Bortoli, Michele
通讯作者：
De Bortoli, Michele
影响因子：
2.7
作者：
Balbo, Silvia;Meng, Lei;Hecht, Stephen S.
通讯作者：
Hecht, Stephen S.