Profiling of the transcriptional response to all-trans retinoic acid in breast cancer cells reveals RARE-independent mechanisms of gene expression.
Profiling of the transcriptional response to all-trans retinoic acid in breast cancer cells reveals RARE-independent mechanisms of gene expression.
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DOI：
10.1038/s41598-017-16687-6
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发表时间：
2017-11-30
影响因子：
4.6
通讯作者：
Marcato P
中科院分区：
文献类型：
--
作者：
Coyle KM;Maxwell S;Thomas ML;Marcato P
类维生素A是维生素A的衍生物，是对细胞分化、增殖和凋亡具有调节作用的关键生理分子。因此，它们对癌症治疗很感兴趣。具体来说，乳腺癌模型对类维生素A信号传导的反应有不同的反应。本研究表征了 MDA-MB-231 和 MDA-MB-468 乳腺癌细胞对视黄醛脱氢酶 1A3 (ALDH1A3) 和全反式视黄酸 (atRA) 的转录反应。我们证明两种细胞系中 ALDH1A3 诱导的基因表达和 atRA 诱导的基因表达之间存在有限的重叠，这表明 ALDH1A3 在乳腺癌进展中的功能超出了其作为视黄醛脱氢酶的作用。我们的数据揭示了对 atRA 的不同转录反应，这些反应在很大程度上独立于基因组视黄酸反应元件 (RARE)，并且与 MDA-MB-231 和 MDA-MB-468 对体内 atRA 治疗的相反反应一致。我们确定与每个基因组相关的转录因子。 IRF1 转录因子的操作表明，atRA 诱导型和表观遗传调控转录因子的水平决定了靶基因（例如 CTSS、组织蛋白酶 S）的表达。这项研究为乳腺癌模型对 atRA 治疗的复杂反应提供了一个范例，并说明了需要在各种模型中表征对 atRA 的 RARE 独立反应。
Retinoids, derivatives of vitamin A, are key physiological molecules with regulatory effects on cell differentiation, proliferation and apoptosis. As a result, they are of interest for cancer therapy. Specifically, models of breast cancer have varied responses to manipulations of retinoid signaling. This study characterizes the transcriptional response of MDA-MB-231 and MDA-MB-468 breast cancer cells to retinaldehyde dehydrogenase 1A3 (ALDH1A3) and all-trans retinoic acid (atRA). We demonstrate limited overlap between ALDH1A3-induced gene expression and atRA-induced gene expression in both cell lines, suggesting that the function of ALDH1A3 in breast cancer progression extends beyond its role as a retinaldehyde dehydrogenase. Our data reveals divergent transcriptional responses to atRA, which are largely independent of genomic retinoic acid response elements (RAREs) and consistent with the opposing responses of MDA-MB-231 and MDA-MB-468 to in vivo atRA treatment. We identify transcription factors associated with each gene set. Manipulation of the IRF1 transcription factor demonstrates that it is the level of atRA-inducible and epigenetically regulated transcription factors that determine expression of target genes (e.g. CTSS, cathepsin S). This study provides a paradigm for complex responses of breast cancer models to atRA treatment, and illustrates the need to characterize RARE-independent responses to atRA in a variety of models.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
DOI：
10.4161/cc.8.20.9761
发表时间：
2009-10-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Ginestier C;Wicinski J;Cervera N;Monville F;Finetti P;Bertucci F;Wicha MS;Birnbaum D;Charafe-Jauffret E
通讯作者：
Charafe-Jauffret E
影响因子：
8
作者：
Fazi, F;Travaglini, L;Nervi, C
通讯作者：
Nervi, C
DOI：
10.1073/pnas.0603806103
发表时间：
2006-08-01
影响因子：
11.1
作者：
Chute, John P.;Muramoto, Garrett G.;McDonnell, Donald P.
通讯作者：
McDonnell, Donald P.
影响因子：
--
作者：
Coyle KM;Murphy JP;Vidovic D;Vaghar-Kashani A;Dean CA;Sultan M;Clements D;Wallace M;Thomas ML;Hundert A;Giacomantonio CA;Helyer L;Gujar SA;Lee PW;Weaver IC;Marcato P
通讯作者：
Marcato P