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首页> 外文期刊>Molecular Cancer >Expression and sub-cellular localization of an epigenetic regulator, co-activator arginine methyltransferase 1 (CARM1), is associated with specific breast cancer subtypes and ethnicity
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Expression and sub-cellular localization of an epigenetic regulator, co-activator arginine methyltransferase 1 (CARM1), is associated with specific breast cancer subtypes and ethnicity

机译：表观遗传调节剂，共激活精氨酸甲基转移酶1（CARM1）的表达和亚细胞定位与特定的乳腺癌亚型和种族有关

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Background Co-Activator Arginine Methyltransferase 1(CARM1) is an Estrogen Receptor (ER) cofactor that remodels chromatin for gene regulation via methylation of Histone3. We investigated CARM1 levels and localization across breast cancer tumors in a cohort of patients of either European or African ancestry. Methods We analyzed CARM1 levels using tissue microarrays with over 800 histological samples from 549 female cancer patients from the US and Nigeria, Africa. We assessed associations between CARM1 expression localized to the nucleus and cytoplasm for 11 distinct variables, including; ER status, Progesterone Receptor status, molecular subtypes, ethnicity, HER2 + status, other clinical variables and survival. Results We found that levels of cytoplasmic CARM1 are distinct among tumor sub-types and increased levels are associated with ER-negative (ER-) status. Higher nuclear CARM1 levels are associated with HER2 receptor status. EGFR expression also correlates with localization of CARM1 into the cytoplasm. This suggests there are distinct functions of CARM1 among molecular tumor types. Our data reveals a basal-like subtype association with CARM1, possibly due to expression of Epidermal Growth Factor Receptor (EGFR) . Lastly, increased cytoplasmic CARM1, relative to nuclear levels, appear to be associated with self-identified African ethnicity and this result is being further investigated using quantified genetic ancestry measures. Conclusions Although it is known to be an ER cofactor in breast cancer, CARM1 expression levels are independent of ER. CARM1 has distinct functions among molecular subtypes, as is indicative of its sub-cellular localization and it may function in subtype etiology. These sub-cellular localization patterns, indicate a novel role beyond its ER cofactor function in breast cancer. Differential localization among ethnic groups may be due to ancestry-specific polymorphisms which alter the gene product.
机译：背景辅助激活剂精氨酸甲基转移酶1（CARM1）是一种雌激素受体（ER）辅助因子，可通过组蛋白3的甲基化来重塑染色质以进行基因调控。我们在欧洲或非洲血统的患者队列中研究了乳腺癌肿瘤中CARM1的水平和定位。方法我们使用组织微阵列分析了来自美国和尼日利亚，非洲的549名女性癌症患者的800多种组织学样品，分析了CARM1水平。我们针对11个不同的变量评估了位于细胞核和细胞质中的CARM1表达之间的关联。 ER状态，孕激素受体状态，分子亚型，种族，HER2 +状态，其他临床变量和生存率。结果我们发现细胞质CARM1的水平在肿瘤亚型之间是不同的，并且水平升高与ER阴性（ER-）状态有关。较高的核CARM1水平与HER2受体状态有关。 EGFR表达还与CARM1定位到细胞质中有关。这表明在分子肿瘤类型之间，CARM1具有不同的功能。我们的数据揭示了可能与表皮生长因子受体（EGFR）的表达相关的与CARM1的基底样亚型。最后，相对于核水平而言，细胞质CARM1的增加似乎与自我认同的非洲种族有关，并且正在使用定量遗传学方法进一步研究这一结果。结论尽管已知它是乳腺癌的ER辅助因子，但CARM1表达水平与ER无关。 CARM1在分子亚型中具有独特的功能，这表明其亚细胞定位，并且可能在亚型病因中起作用。这些亚细胞定位模式表明在乳腺癌中除了其ER辅助因子功能以外，还有新的作用。族裔之间的差异化定位可能是由于祖先特定的多态性改变了基因产物。

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