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芝加哥乳腺癌队列研究中乳腺癌病例的糖皮质激素受体基因变异与免疫组化定位

Genetic Variation and Immunohistochemical Localization of the Glucocorticoid Receptor in Breast Cancer Cases from the Breast Cancer Care in Chicago Cohort.

作者信息

Al-Alem Umaima, Mahmoud Abeer M, Batai Ken, Shah-Williams Ebony, Gann Peter H, Kittles Rick, Rauscher Garth H

机构信息

Division of Epidemiology and Biostatistics, University of Illinois at Chicago, Chicago, IL 60612, USA.

Department of Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.

出版信息

Cancers (Basel). 2021 May 13;13(10):2261. doi: 10.3390/cancers13102261.

Abstract

BACKGROUND

Glucocorticoid, one of the primary mediators of stress, acts via its receptor, the glucocorticoid receptor (), 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 , , , , , , , , and .

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.

摘要

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)发挥作用,调节众多生理过程。我们测量了GCR的基因变异和蛋白表达,以及调节GCR功能或反应的基因,并研究了这些改变是否与乳腺癌的临床病理特征相关。

方法

我们使用来自多种族乳腺癌患者队列的样本,评估乳腺癌特征与GCR、FKBP5、HSP90AB1、NR3C1、PPID、RACK1、S100A1、SEPP1和TFF1中单核苷酸多态性(SNP)的基因变异之间的关联。

结果

几个SNP与乳腺癌特征相关,但在进行多重比较校正后,统计学显著性消失。在所有正常乳腺组织中均检测到GCR,且主要位于肌上皮细胞层的细胞核中,而腔层GCR呈阴性。与非肿瘤组织相比,所有乳腺癌组织类型中GCR表达均显著降低,但与乳腺癌特征无关。我们发现高核GCR表达与基底细胞标志物细胞角蛋白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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2566/8152982/e2559e690238/cancers-13-02261-g001.jpg

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