Genetic Variation and Immunohistochemical Localization of the Glucocorticoid Receptor in Breast Cancer Cases from the Breast Cancer Care in Chicago Cohort.
Genetic Variation and Immunohistochemical Localization of the Glucocorticoid Receptor in Breast Cancer Cases from the Breast Cancer Care in Chicago Cohort.
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DOI：
10.3390/cancers13102261
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发表时间：
2021-05-13
期刊：
影响因子：
5.2
通讯作者：
Rauscher GH
中科院分区：
文献类型：
--
作者：
Al-Alem U;Mahmoud AM;Batai K;Shah-Williams E;Gann PH;Kittles R;Rauscher GH
乳腺癌是女性死亡的主要原因之一，是一种复杂的疾病，心理社会压力等多种因素与乳腺癌的发生和进展有关。糖皮质激素受体（GCR）是将压力信号传递到体内的分子之一。我们测量了 GCR 的遗传变异和蛋白质表达以及调节 GCR 功能或反应的基因，并检查这些变异是否与乳腺癌相关。我们发现了一些功能上重要的 SNP 的遗传变异，这些变异与疾病的晚期阶段、更高的级别和激素受体阴性状态相关。乳腺癌组织中GCR蛋白表达降低并与基底细胞标志物CK5/6相关。背景：糖皮质激素是应激的主要介质之一，通过其受体糖皮质激素受体 (GCR/NR3C1) 发挥作用，调节多种生理过程。我们测量了 GCR 的遗传变异和蛋白表达，以及调节 GCR 功能或反应的基因，并检查这些改变是否与乳腺癌临床病理特征相关。方法：我们使用来自多种族乳腺癌患者队列的样本来评估乳腺癌特征与 GCR/NR3C1、FKBP5、Sgk1、IL-6、ADIPOQ、LEPR、SOD2、CAT 和 BCL2 中单核苷酸多态性 (SNP) 遗传变异之间的关联。结果：多个 SNP 与乳腺癌特征相关，但在调整多重比较后统计显着性消失。在所有正常乳腺组织中均检测到 GCR，并且主要位于肌上皮细胞层的细胞核，而管腔层 GCR 呈阴性。与非肿瘤组织相比，所有乳腺癌组织类型中 GCR 表达均显着降低，但与乳腺癌特征无关。我们发现高核 GCR 表达与基底细胞标记物细胞角蛋白 5/6 阳性相关。结论：乳腺癌组织中GCR表达降低，且与基底细胞标志物CK5/6相关。
Breast cancer, one of the leading causes of death among women, is a complex disease in which several factors, such as psychosocial stress, have been implicated in its initiation and progression. The glucocorticoid receptor (GCR) is one of the molecules that transfers the stress signal into the body. We measured the genetic variation and protein expression of GCR and the genes that regulate GCR function or response and examined whether these variations were associated with breast cancer. We found several genetic variants of functionally important SNPs associated with later disease stage, higher grade, and hormone receptor-negative status. The GCR protein expression was reduced in breast cancer tissue and correlated with the basal cell marker CK5/6. Background: Glucocorticoid, one of the primary mediators of stress, acts via its receptor, the glucocorticoid receptor (GCR/NR3C1), to regulate a myriad of physiological processes. We measured the genetic variation and protein expression of GCR, and the genes that regulate GCR function or response and examined whether these alterations were associated with breast cancer clinicopathological characteristics. Method: We used samples from a multiracial cohort of breast cancer patients to assess the association between breast cancer characteristics and the genetic variants of single nucleotide polymorphisms (SNPs) in GCR/NR3C1, FKBP5, Sgk1, IL-6, ADIPOQ, LEPR, SOD2, CAT, and BCL2. Results: Several SNPs were associated with breast cancer characteristics, but statistical significance was lost after adjustment for multiple comparisons. GCR was detected in all normal breast tissues and was predominantly located in the nuclei of the myoepithelial cell layer, whereas the luminal layer was negative for GCR. GCR expression was significantly decreased in all breast cancer tissue types, compared to nontumor tissue, but was not associated with breast cancer characteristics. We found that high nuclear GCR expression was associated with basal cell marker cytokeratin 5/6 positivity. Conclusion: GCR expression is reduced in breast cancer tissue and correlates with the basal cell marker CK5/6.
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Lillberg, K;Verkasalo, PK;Koskenvuo, M
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