Treatment with the cancer drugs decitabine and doxorubicin induces human skin keratinocytes to express Oct4 and the OCT4 regulator mir-145.
Treatment with the cancer drugs decitabine and doxorubicin induces human skin keratinocytes to express Oct4 and the OCT4 regulator mir-145.
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DOI：
10.1111/j.1346-8138.2012.01553.x
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发表时间：
2012-07
期刊：
影响因子：
--
通讯作者：
Bickenbach JR
中科院分区：
文献类型：
--
作者：
Chinnathambi S;Wiechert S;Tomanek-Chalkley A;Winter MC;Bickenbach JR
在此之前，我们发现OCT4瞬时转染不仅在皮肤角质形成细胞中产生了Oct4的高表达，而且还导致了角质形成细胞DNA的普遍去甲基化。我们假设仅DNA去甲基化可能允许内源性OCT4的表达。在这里，我们报道了抗癌药物地西他滨治疗导致皮肤角质形成细胞普遍的DNA去甲基化，治疗48小时后，96%的角质形成细胞显示内源性Oct4蛋白和OCT4抑制因子145的表达。这只对角质形成细胞是正确的，因为同样处理的皮肤成纤维细胞没有OCT4或mir-145的表达。地西他滨处理的角质形成细胞也表现出类似于其他Oct4+细胞的mir-302C增加和增殖。用另一种抗癌药物阿霉素治疗，只在已经表达OCT4的细胞中诱导mir-145的表达，这表明Oct4调节自己的抑制物。与地西他滨和阿霉素联合治疗首先导致OCT4和mir-145升高，然后两者都降低，这表明OCT4和mir-145相互调节。这种新的策略为转化研究提供了一个可调节的系统来生产Oct4+细胞，并为研究内源性Oct4在癌细胞和周围体细胞中的作用提供了一种独特的方法。
Previously, we showed that transient transfection with OCT4 not only produced high expression of Oct4 in skin keratinocytes, but also caused a generalized demethylation of keratinocyte DNA. We hypothesized that DNA demethylation alone might allow expression of endogenous OCT4. Here, we report that treatment with the cancer drug decitabine results in generalized DNA demethylation in skin keratinocytes, and by 48 hours after treatment, 96% of keratinocytes show expression of the endogenous Oct4 protein and the OCT4 repressor mir-145. This is true for keratinocytes only, as skin fibroblasts treated similarly show no OCT4 or mir-145 expression. Decitabine-treated keratinocytes also show increased mir-302c and proliferation similar to other Oct4+ cells. Treatment with doxorubicin, another cancer drug, induces expression of mir-145 only in cells that already express OCT4, suggesting that Oct4 regulates its own repressor. Co-treatment with decitabine and doxorubicin results first in increased OCT4 and mir-145, then a decrease in both, suggesting that OCT4 and mir-145 regulate each other. The novel strategy presented here provides a regulatable system to produce Oct4+ cells for transformation studies and provides a unique method to study the effects of endogenous Oct4 in cancer cells and the surrounding somatic cells.
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影响因子：
30.8
作者：
Wang, Yangming;Baskerville, Scott;Shenoy, Archana;Babiarz, Joshua E.;Baehner, Lauren;Blelloch, Robert
通讯作者：
Blelloch, Robert
影响因子：
11.2
作者：
Wang Y;Blelloch R
通讯作者：
Blelloch R
影响因子：
4.5
作者：
Lin, Shi-Lung;Chang, Donald C.;Ying, Shao-Yao
通讯作者：
Ying, Shao-Yao
DOI：
10.1073/pnas.0808042106
发表时间：
2009-03-03
影响因子：
11.1
作者：
Sachdeva, Mohit;Zhu, Shoumin;Mo, Yin-Yuan
通讯作者：
Mo, Yin-Yuan
影响因子：
64.8
作者：
Hatfield, SD;Shcherbata, HR;Ruohola-Baker, H
通讯作者：
Ruohola-Baker, H